Report to Congress 

Coordinated Strategy to 

Accelerate Development of 

Vaccines for Infectious Diseases 

October 2009 
Report to Congress 

COORDINATED STRATEGY 

TO ACCELERATE DEVELOPMENT 

OF VACCINES FOR INFECTIOUS DISEASES 

October 2009 

Table of Contents 

Acronyms and Abbreviations ........................................................................................................................ i
 

Executive Summary ...................................................................................................................................... 1
 

I. Introduction ............................................................................................................................................... 7
 

II. Background on Vaccine Development and the Role of the U.S. Government ........................................ 9
 

III. Current Investments and Activities for the Development of Vaccines ................................................. 11
 

IV. Initiatives to Create Incentives for the Research, Development and Manufacturing of Vaccines ........ 35
 

V. Expansion of Public-Private Partnerships and Leveraging Resources 

 from Other Countries and the Private Sector ........................................................................................... 41
 

VI. Efforts to Maximize United States Capabilities to Support Clinical Trials of Vaccines 

 in Developing Countries and to Address the Challenges of Delivering Vaccines 

in the Developing Countries .................................................................................................................... 47
 

VII. Coordinated Strategy........................................................................................................................... 53
 

Acronyms and Abbreviations 

AAVP African AIDS Vaccine Program 

ACTG AIDS Clinical Trials Group 

AIDS Acquired Immune Deficiency Syndrome 

AMC Advance Market Commitments 

AVRS AIDS Vaccine Research Subcommittee 

BCG Bacille Calmette Guerin (childhood vaccine for Tuberculosis) 

BMFG Bill & Melinda Gates Foundation 

CHAVI Center for HIV/AIDS Vaccine Immunology 

CDC Centers for Disease Control and Prevention 

DHHS Department of Health and Human Services 

DHP Defense Health Program 

DoD Department of Defense 

DOTS Directly Observed Treatment, Short Course 

EPI Expanded Program on Immunization 

FIC Fogarty International Center 

GAVI GAVI Alliance (formerly Global Alliance for Vaccines and Immunization) 

GSK GlaxoSmithKline 

HepB Hepatitis B 

Hib Haemophilus influenzae type b 

HIV Human Immunodeficieny Virus 

HIVRAD HIV Research and Design 

HVTN HIV Vaccine Trial Network 

IAVI International AIDS Vaccine Initiative 

IDCRP Infectious Disease Clinical Research Program 

IDRI Infectious Disease Research Institute 

IOM Institute of Medicine 

LMIV Laboratory of Malaria Immunology and Vaccinology 

LMVR Laboratory of Malaria and Vector Research 

MIDRP Military Infectious Disease Research Program 

MHRP U.S. Military HIV Research Program 

MMVDP Military Malaria Vaccine Development Program 

MRC Medical Research Council (of South Africa) 

MVDP Malaria Vaccine Development Program 

i 
MVI Malaria Vaccine Initiative 

MVP Malaria Vaccine Project 

NCRR National Center for Research Resources 

NCI National Cancer Institute 

NGO Nongovernmental Organization 

NIAID National Institute of Allergy and Infectious Diseases 

NICHD National Institute of Child Health and Human Development 

NIDCR National Institute of Dental and Craniofacial Research 

NIH National Institutes for Health 

NMRC Naval Medical Research Center 

NTD Neglected Tropical Diseases 

OAR Office of AIDS Research 

PAVE Partnership for AIDS Vaccine Evaluation 

PDP Product Development Partnership 

PEPFAR President’s Emergency Plan for AIDS Relief 

PRV Priority Review Voucher 

R&D Research and Development 

SAAVI South African Vaccine Initiative 

SVEU Simian Vaccine Evaluation Unit 

TB Tuberculosis 

UNAIDS The Joint United Nations Program on HIV/AIDS 

USAID U.S. Agency for International Development 

U.S. FDA U.S. Food and Drug Administration 

USG U.S. Government 

VRC Vaccine Research Center 

WHO World Health Organization 

WRAIR Walter Reed Army Institute of Research 

ii 
Executive Summary 

The purpose of the Tom Lantos and Henry J. Hyde United States Global Leadership against HIV/AIDS, 

Tuberculosis, and Malaria Reauthorization Act of 2008, Public Law 110-293, is to strengthen and 

enhance U.S. leadership and the effectiveness of the U.S. response to the HIV/AIDS, tuberculosis, and 

malaria pandemics and other related and preventable infectious diseases as part of the overall U.S. health 

and development agenda. 

Section 206 of this law states: “the President shall produce a comprehensive report, written by a study 

group of qualified professionals from relevant Federal agencies and initiatives, nongovernmental 

organizations, and industry representatives, that sets forth a coordinated strategy to accelerate 

development of vaccines for infectious diseases, such as HIV/AIDS, malaria, and tuberculosis, which 

includes: 

i.	 initiatives to create economic incentives for the research, development, and 

manufacturing of vaccines for HIV/AIDS, tuberculosis, malaria, and other infectious 

diseases; 

ii.	 an expansion of public-private partnerships and the leveraging of resources from other 

countries and the private sector; and 

iii.	 efforts to maximize United States capabilities to support clinical trials of vaccines in 

developing countries and to address the challenges of delivering vaccines in developing 

countries to minimize delays in access once vaccines are available.” 

This comprehensive report responds to this request. This report was compiled and edited by the 

congressionally mandated study group, which was set up for this purpose. The group met face-to-face on 

August 12, 2009 and worked virtually in the preparation of this report between July 2009 and September 

2009. The study group includes professionals from the U.S. Agency for International Development 

(USAID), the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), 

the National Vaccine Program Office of the Department of Health and Human Services, the Department 

of Defense (DoD), the Department of Treasury, The Program for Applied Technology in Health (PATH), 

the National AIDS Vaccine Initiative (IAVI), Aeras Global TB Vaccine Foundation, the Center for 

Global Development, the Bill & Melinda Gates Foundation (BMGF), and Merck & Co. 

Coordinated Strategy to Accelerate the Development 

of Vaccines for Infectious Diseases 

The U.S. Government is engaged in coordinated strategies with partners the world over to accelerate 

development of vaccines for infectious diseases such as HIV/AIDS, malaria, and tuberculosis, and to 

deliver vaccines to people in developing countries. Each agency’s mandate, funding levels, and 

availability of expertise determine where they engage on the continuum from basic research through 

delivery and immunization in developing countries. 

HIV/AIDS Vaccine Development Summary 

The U.S. Government (USG) is committed to the discovery and testing of a vaccine capable of preventing 

HIV and controlling the AIDS pandemic. The USG efforts to this end are, in large part, through 

collaborations with other governments, industry partners, foundations like the BMGF, and 

nongovernmental organizations, and key biotech sub-partners. The Enterprise (a consortium of 

independent organizations committed to accelerating the development of an HIV vaccine), as a nonprescriptive but neutral and unifying voice for the field, provides the structure to prioritize the scientific 

agenda, avoid duplication of efforts, and maintain the focus and momentum to design and develop the 

most promising HIV vaccine candidates. The Partnership for AIDS Vaccine Evaluation (PAVE) is 

another voluntary consortium of the USG agencies and USG-funded organizations involved in HIV 

1 
 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

vaccine research. Members of PAVE include the National Institutes of Allergy and Infectious Diseases 

(NIAID), Office of AIDS Research (OAR), the NIAID-funded HIV Vaccine Trials Network (HVTN), 

USAID, the U.S. Military HIV Research Program (MHRP), CDC, and IAVI. 

In 2008, total global investment in HIV vaccine research and development (R&D) was US$868 million, a 

US$93million (10%) decrease from the previous year, as reported by the HIV Vaccines and Microbicides 

Resource Tracking Working Group.1

 Public-sector funders provided 85% (US$731 million) of those 

investments, the philanthropic sector 11% (US$104 million), and the commercial sector 4% (US$33 

million). The USG is the leading donor, having invested US$620 million in 2008. The philanthropic 

sector accounted for US$104 million or about 12% of the total funds disbursed for HIV Vaccine R&D in 

2008. The BMGF and the Wellcome Trust together accounted for 91% of all philanthropic investments. 

Total investment by the commercial sector (pharmaceutical and biotechnology companies) in HIV 

vaccine development in 2008 was estimated at US$33 million (range US$18 million to US$45 million), a 

decline of 61% from 2007 levels. 

The search for products has been challenging. In efficacy studies, two vaccine candidates have not shown 

they protect against HIV infection or moderate subsequent HIV disease. A third vaccine entered advanced 

clinical evaluation in June 2009. As announced in September 2009, a fourth vaccine studied for efficacy 

in Thailand on 16,402 participants has reported efficacy of 31% in an historic first-time result proving a 

concept that is sure to lead to improved vaccine candidates. The vaccine studied in Thailand was the first 

evidence of an HIV vaccine providing any level of protection against HIV infection. Statistical analyses 

presented as part of their initial announcement support the validity of the finding. The trial was a “test of 

concept” study designed to identify initial signs of promise in a product. The trial sponsors and 

implementers led by the U.S. Military HIV Research Program and funded by NIAID, included the U.S. 

Army, the Thai Ministry of Public Health, Sanofi Pasteur, and Global Solutions for Infectious Diseases. 

The collaborators will be conducting additional studies to further understand these positive results. 

The recent findings in Thailand have important implications for the design of future HIV vaccines and 

how they are tested; however, additional research is needed to better understand how this vaccine regimen 

reduced the risk of HIV infection. In addition, scientific advances in defining how the human immune 

system attempts to protect itself against HIV are unfolding. The earliest events in natural infection, 

particularly in those that show an immune capacity to resist the virus, are beginning to inform new 

vaccine design; translating these events into a candidate vaccine holds great promise to have an impact on 

the epidemic with an eventually licensable vaccine. 

Tuberculosis Vaccine Development Summary 

The USG is the largest bilateral donor supporting the implementation of biomedical TB research and TB 

control programs in disease-endemic countries. USG-funded research and support have long been one of 

the only means by which development of vaccine candidates for TB has been facilitated. In 2007, total 

spending for TB vaccine research was US $410 million, of which US $323 million was USG-funded 

research. NIH, through NIAID, is the lead agency for biomedical TB research, including vaccine-related 

research. As of 2008, NIAID was the largest funder of biomedical TB research, with an annual budget of 

more than US$120 million and the second largest funder for TB vaccine R&D. While NIH/NIAID’s 

mission is focused on fundamental and translational biomedical research that includes the preclinical and 

early clinical evaluation of new vaccines, development of new health care interventions requires the 

stewardship and support of pharmaceutical companies. Other USG organizations will be critical to 

facilitate introduction of vaccines and evaluate field effectiveness and will play an important role in 

completing epidemiological studies to enable late-stage and post-licensure trials. 

1

 The Resource Tracking Working Group was established in 2004 to generate and disseminate high-quality, detailed and 

comparable data on global investments in preventive HIV vaccine and microbicide research and development (R&D), policy and 

advocacy activities. 

2 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

The Bill & Melinda Gates Foundation recently established several not-for profit organizations to facilitate 

development and implementation of new drugs, vaccines, and diagnostics that may be developed through 

academic, for-profit, or other not-for profit organizations. These organizations (the Global Alliance for 

TB Drug Development, the Aeras Global TB Vaccine Foundation, and the Foundation for Innovative 

New Diagnostics) have facilitated the transition of many product candidates and tools that were initially 

developed with USG funding into advanced-stage clinical testing. 

There are several strategies being pursued worldwide to develop new vaccine candidates and approaches 

for TB, including: 

1.	 Recombinant BCG 

2.	 Virally vectored TB vaccines 

3.	 Adjuvanted subunit vaccines 

4.	 DNA vaccines 

5.	 Other approaches – to expand the diversity of vaccine candidates and approaches, scientists are 

also evaluating the feasibility of attenuating Mycobacterium tuberculosis (Mtb) through multiple 

gene deletions to serve as safe, immunogenic vaccines or platforms for advanced vaccination 

strategies 

Coordination among the various global vaccine development entities and private partners is implemented 

through the Stop TB Partnership’s Working Group on New Vaccines. Furthermore, coordination among 

the various partners is accomplished through continual interaction, mutual consultations, workshops, 

development of milestones, and leveraging of available resources. Since clinical vaccine candidates for 

TB have only recently emerged, additional collaboration will be needed to facilitate advanced clinical 

development and field evaluation. 

To contribute effectively to TB control programs worldwide, strategies for combining drugs and vaccines 

to either enhance efficacy or shorten chemotherapy for adult and pediatric patients will likely be 

considered. To facilitate the development of advanced vaccination strategies, more sophisticated animal 

model, immune, and natural disease history protocols will need to be established and validated. The 

introduction of new TB vaccines will also require tight coordination with TB and HIV control programs 

to assure the most appropriate use of novel adult or adolescent boosting vaccines, as well as to inform 

strategies for improving neonatal TB vaccination. All current and future USG TB vaccine R&D efforts 

are and will continue to be leveraged with European and other global vaccine development efforts to 

avoid duplication and assure maximum use of limited resources. 

Malaria Vaccine Development Summary 

U.S. Government agencies have been leaders for more than four decades in efforts to develop a malaria 

vaccine to mitigate the enormous loss of life, illness, and economic burden of malaria in the developing 

world. Working both internally and with nongovernmental organizations (NGOs), academic institutions, 

and commercial companies, these efforts have resulted in major advances in the understanding of the 

biology of malaria and in the clinical development of many vaccines, one of which has entered Phase III 

evaluation. Both the Military Malaria Vaccine Program (MMVP), consisting of the U.S. Army Walter 

Reed Army Institute of Research (WRAIR) and the Naval Medical Research Center (NMRC), and the 

USAID Malaria Vaccine Development Program (MVDP) have focused on such product development. 

NIAID also has made major strategic research contributions. 

At this writing, GlaxoSmithKline Biologicals (GSK) is fielding a large multicenter trial of a malaria 

vaccine, funded by the BMGF and managed by the Malaria Vaccine Initiative at PATH (MVI). Although 

this trial is made possible through the BMGF, the scientific basis and development of the vaccine is 

directly attributable to USG programs, principally that of WRAIR. This vaccine has the potential to have 

significant impact on malaria morbidity and mortality if it achieves licensure. However, it may not be 

3 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

effective enough to prevent malaria entirely in an immunized population. Next-generation vaccines are 

badly needed, and the USG malaria vaccine development effort is focused on this goal. 

Most of the current U.S. Government malaria vaccine development effort is through the following 

approaches: 

1.	 Development of new vaccines based on the target molecule used in the GSK vaccine 

2.	 Heterologous or “prime boost” immunization 

3.	 Blood stage vaccines 

4.	 Combination vaccines (Sound reasoning suggests that a combination of more than one parasite 

component will need to be employed in order to develop highly efficacious malaria vaccines, and 

this is reflected in the USG strategy.) 

5.	 New target discovery 

Coordination among the various USG agencies and private partners takes place through liaison on a daily 

basis. In addition, the Federal Malaria Vaccine Coordinating Committee (FMVCC) meets at irregular 

intervals for general coordination or consideration of special topics requiring attention. As needed, 

FMVCC invites nongovernment partners to participate. 

The USG malaria vaccine development effort will continue to work collaboratively both inside and 

outside the USG toward the goal of practical vaccines to control malaria in the developing world. Efforts 

not managed by the USG will be watched with interest and the USG strategy modified as new 

information becomes available. Specific new approaches will be selected and added to the portfolio, 

based on the best scientific information available. Approaches will be accelerated if shown to be 

promising or discarded if not. The USG program will remain cognizant of the changing epidemiology of 

malaria and adjust accordingly. The rate of progress will be proportional to resources available. 

Other Infectious Diseases 

While HIV/AIDS, malaria and tuberculosis are priorities in vaccine research because of their worldwide 

prevalence and high mortality rates, the USG also aims to identify new vaccine candidates for many other 

diseases, such as neglected tropical diseases, enteric diseases, and dengue fever. Investigators are working 

to make these vaccines safer and effective for the targeted populations, including those with compromised 

immune systems. 

Neglected tropical diseases (NTDs) represent the most common infections of the world’s one billion 

poorest people and include a group of chronic parasitic and bacterial infections such as hookworm 

infection, ascariasis, schistosomiasis, lymphatic filariasis, onchocerciasis, Chagas disease, leishmaniasis, 

and trachoma. Robust vaccine research studies directed at many of these serious and pervasive illnesses 

are ongoing at NIH in its intramural and extramural research programs. Through the DoD’s NMRC and 

WRAIR, the USG is focusing its efforts to develop preventive vaccines against Shigella, enterotoxigenic 

E coli (ETEC), and Campylobacter, three leading bacterial causes of traveler’s diarrhea. WRAIR and 

NMRC also have well coordinated efforts to develop a dengue vaccine. Through DoD in-house efforts as 

well as co-development relationships with extramural partners, WRAIR and NMRC are participating in 

the development and assessment of six candidate vaccines, three of which are in human trials and one in 

advanced development with a major pharmaceutical partner. The DoD is sponsoring the only attempt to 

develop an FDA-licensed vaccine for hemorrhagic fever with renal syndrome HFRS, a potentially fatal 

hantavirus. The DoD is also providing limited support to develop a vaccine that will protect troops from 

scrub typhus. 

The USG will continue to collaborate with public-private organizations in efforts to develop vaccines for 

other infectious diseases, such as neglected tropical diseases, enteric diseases, and dengue fever. The great 

majority of these efforts are currently in the basic research and preclinical phases, although it is 

anticipated that some of them will move into the clinical phase in coming years. 

4 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Initiatives to Create Economic Incentives for the Research, 

Development, and Manufacturing of Vaccines for HIV/AIDS, 

Tuberculosis, Malaria, and Other Infectious Diseases 

There are a range of incentives and innovative financing mechanisms such as Advanced Market 

Commitments (AMC) in early phases of implementation and others that are being explored. These 

mechanisms have the potential to stimulate accelerated research and development of vaccines. However, 

before increased commitment by the USG, the various mechanisms require further study to determine 

which mechanisms are most appropriate and feasible for investment. The USG will continue to consider 

options specific to U.S.-based R&D and manufacturing, while monitoring the progress of the pilot 

Advanced Market Commitment and other economic incentives. 

An Expansion of Public-Private Partnerships and the Leveraging of 

Resources from Other Countries and the Private Sector 

USG agencies are engaged with a variety of partners from academia, industry, UN agencies, civil society, 

developing countries, and product development partnerships (PDPs). An expansion of public-private 

partnerships and the leveraging of resources from other countries and the private sector could accelerate 

the development of vaccines. The variety and number of current PDPs make it necessary to determine 

whether additional PDPs are required to accelerate the development of vaccines or whether the need lies 

in expanding existing PDPs. As such, as part of the USG strategy to accelerate the research, development 

and manufacturing of vaccines, the U.S. Government will explore the range of vaccine development 

partnerships to determine the most efficient way for the USG to leverage private-sector expertise with 

scarce resources and strategically engage in supporting the indirect determinants around market 

preparation. 

Efforts to Maximize U.S. Capabilities to Support Clinical Trials of 

Vaccines in Developing Countries and to Address the Challenges of 

Delivering Vaccines in Developing Countries to Minimize Delays in 

Access Once Vaccines Are Available 

USG agencies engaged in vaccine R&D and immunization delivery are well coordinated and work 

strategically within individual vaccine areas. However, across vaccine areas more information-sharing 

and joint strategic development need to take place. The USG has actively developed sustainable clinical 

trial sites in the developing world over many years and works to continue to make those sites more robust, 

as the more complex clinical trials for vaccines against more complex diseases are required. To accelerate 

the development of vaccines, the USG will build upon what was accomplished by PAVE for HIV vaccine 

trial sites and will conduct a mapping exercise of all vaccine clinical sites that are implemented by or 

funded by the USG. More robust information on the relevant clinical trial sites will lead to more 

strategically coordinated, streamlined, and aligned government support for advancing the development of 

new vaccines for infectious diseases. Delivering vaccines in developing countries is complex. Public 

health impact is not achieved when the vaccine is developed but rather when it reaches the intended 

population in developing countries. The U.S. Government will continue to program in a strategic and 

complementary fashion to build immunization program capacity in developing countries. 

In order to coordinate the acceleration of the development of vaccines for infectious diseases, USG 

agencies will continue to convene a study group or groups around the strategy to further engage across 

disease-specific areas. Each U.S. Government agency engaged in global health research plays a distinct 

role at different stages of research, and nongovernmental partners provide unique expertise in vaccine 

development. For this reason, a study group or groups will meet at regular intervals to continue 

collaboration to accelerate vaccine development, to share information on vaccine development efforts, 

5 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

and to maximize the synergies that are created from working in a more coordinated manner. The rate of 

progress in each area of vaccine research, development, and delivery will be proportional to resources 

available. 

6 
I. Introduction 

The purpose of the Tom Lantos and Henry J. Hyde United States Global Leadership against HIV/AIDS, 

Tuberculosis, and Malaria Reauthorization Act of 2008, Public Law 110-293, is to strengthen and 

enhance U.S. leadership and the effectiveness of the U.S. response to the HIV/AIDS, tuberculosis, and 

malaria pandemics and other related and preventable infectious diseases as part of the overall U.S. health 

and development agenda. 

Section 206 of this law states: “the President shall produce a comprehensive report, written by a study 

group of qualified professionals from relevant Federal agencies and initiatives, nongovernmental 

organizations, and industry representatives, that sets forth a coordinated strategy to accelerate 

development of vaccines for infectious diseases, such as HIV/AIDS, malaria, and tuberculosis, which 

includes: 

i.	 initiatives to create economic incentives for the research, development, and 

manufacturing of vaccines for HIV/AIDS, tuberculosis, malaria, and other infectious 

diseases; 

ii.	 an expansion of public-private partnerships and the leveraging of resources from other 

countries and the private sector; and 

iii.	 efforts to maximize United States capabilities to support clinical trials of vaccines in 

developing countries and to address the challenges of delivering vaccines in developing 

countries to minimize delays in access once vaccines are available.” 

This comprehensive report responds to this request. This report was compiled and edited by the 

congressionally mandated study group, which was set up for this purpose. The group met face-to-face on 

August 12, 2009, and worked virtually in the preparation of this report between July 2009 and September 

2009. The study group includes professionals from the U.S. Agency for International Development 

(USAID), the National Institutes for Health (NIH), the Centers for Disease Control and Prevention 

(CDC), the National Vaccine Program Office of the Department of Health and Human Services, the 

Department of Defense (DoD), the Department of Treasury, PATH, the International AIDS Vaccine 

Initiative, Aeras Global TB Vaccine Foundation, the Center for Global Development, the Bill & Melinda 

Gates Foundation (BMGF), and Merck & Co. 

Section II of this report includes background on vaccine development. Section III provides a summary 

overview of the U.S. strategy for malaria, HIV/AIDS, tuberculosis, and other infectious diseases. Section 

IV discusses initiatives to create economic incentives for the research and development (R&D) of 

vaccines. Section V discusses the role of public-private partnerships and the leveraging of resources from 

other countries. Section VI provides a summary of the role that the United States Government (USG) 

plays in supporting clinical trials in developing countries and also provides an overview of current efforts 

to overcome challenges associated with vaccine delivery. And, Section VII provides a summary of the 

future direction of the USG vaccine development strategy. 

7 

 

II. Background on Vaccine Development 

and the Role of the U.S. Government 

AIDS, tuberculosis, and malaria account for approximately 5 million deaths a year. However, there is no 

proven vaccine for any of these three diseases, and there is great variation in the stages of R&D among 

the vaccines currently under development. This is in large part attributed to the highly complex science 

required to develop vaccines against these infectious diseases. 

The cost of bringing new vaccines to market is substantial and includes costs for animal model studies, 

preclinical studies, clinical trials, licensing, and start-up. Estimates of the total costs associated with 

vaccine development range from several hundred million dollars for basic vaccines to more than US$1.5 

billion2

 for complex vaccines; costs could exceed these expectations for a vaccine against a disease as 

complicated as HIV. About 70% of R&D costs for a typical drug are incurred after clinical trials begin3 

vaccine trials are often larger and more expensive than those for other products. 

The global community must ensure that the needs of both developed and developing countries are taken 

into account when developing new vaccines. The science that underlies vaccine discovery and 

development for diseases of the developing world is largely dependent on scientists in academic, 

government, and private research institutions. Vaccine studies focus on a broad spectrum of R&D 

challenges ranging from the need for an improved understanding of host/pathogen interaction and 

protective immune response to determining which formulation will maintain the viability of heat sensitive 

products for use in areas where refrigeration is scarce. 

A significant share of basic scientific research for health conditions that affect affluent countries is also 

funded by the public sector, while the greater part of product development and clinical trials are typically 

financed by private sector investments. Public investment is thus complemented by commercial 

investments where the promise of a market exists; the largest single source of funding for R&D is the 

commercial sector. There is less funding for R&D of products that address health problems in developing 

countries than for products for developed countries. Overall, only a small proportion of total R&D for 

drugs and vaccines address health problems that disproportionately affect developing countries – about 

US$6 billion of a total of more than US$100 billion annually; of that, less than US$1 billion is devoted to 

vaccine research.4

 Almost all of these funds are from public and philanthropic sources. Commercial 

investments by large pharmaceutical companies are rare because the potential market for these products is 

likely to be insufficient to provide adequate financial returns to cover the costs of development and a 

return on investment. Commercial development of new vaccines for developing countries is driven by the 

same incentives and commercial imperatives facing manufacturers in developed countries. 

Product development research, including that for vaccines, occurs in four broad phases: (I) fundamental 

research, or discovery, defined as research geared toward providing a scientific foundation for the 

understanding of host/pathogen interactions (e.g., malaria pathogenesis and host-immune response to the 

various disease stages); (II) translational research to identify points of intervention, early-stage product 

candidates, as well as needed tools and assays for clinical testing, based on the fundamental knowledge 

acquired in the first phase; (III) product development, which starts with the selection of a clinical 

candidate, preclinical studies to gain regulatory and ethical approval for safety and efficacy studies in 

humans, clinical development (Phases I through III), and licensure and marketing; and (IV) postmarketing, which includes clinical and epidemiological research to evaluate the impact of a newly 

introduced product on the burden of disease. 

2 Making Markets for Vaccines: Ideas to Action, The report of the Center for Global Development, Advance Market Commitment 

Working Group, http://www.cgdev.org/doc/books/vaccine/MakingMarkets-complete.pdf, page 12. 3 Making Markets for Vaccines: Ideas to Action, page 18. 4

 Ibid. 

9 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Vaccine development is often incorrectly described as a linear process in which a vaccine transitions 

without interruption from concept through clinical trials to marketing. However, product development, 

including development of vaccines, usually is an iterative process with a high level of attrition where 

product candidates often fail to meet criteria for advancement at one of the stages in the development 

process and are either abandoned or modified and re-tested. 

U.S. Government agencies have been and continue to be leaders in efforts to develop vaccines against 

HIV, malaria, and tuberculosis. The USG vaccine development effort includes NIH, DoD, USAID, and 

CDC. Each agency has a unique role within the vaccine development pipeline (see Figure 1 above). 

Within the government, the NIH supports basic research, preclinical testing in animal models, 

development of candidate vaccine products, and clinical testing of vaccines at intramural and extramural 

research programs at several institutes and centers. Through the Walter Reed Army Institute of Research 

(WRAIR), the U.S. Army, and the U.S. Navy, the DoD supports preclinical and clinical research, 

epidemiological research of vaccines, primarily for military personnel. CDC supports clinical trials, field 

preparedness, epidemiological research and surveillance, as well as technical assistance to evaluate, 

monitor, and strengthen the delivery of vaccines in the field. USAID supports preclinical testing in animal 

models, development of candidate vaccines products, clinical testing of vaccines, operations research, 

activities to prepare for the introduction of new vaccines, immunization programs, demand forecasting 

and supply, procurement, and logistics. 

AGENCY/INITIATIVE ROLE IN VACCINE DEVELOPMENT 

National Institutes of 

Health (NIH) 

Supports basic research, preclinical testing in animal models, development of candidate 

vaccine products, and clinical testing of vaccines 

Department of Defense 

(DoD) 

Supports basic research, preclinical testing in animal models, development of candidate 

vaccine products, and clinical testing of vaccines 

Centers for Disease 

Control and Prevention 

(CDC) 

Supports clinical trials, field preparedness, epidemiological research, surveillance; 

provides data on disease burden to establish baseline, monitor impact, and track specific 

changes in serotypes as necessary; supports economic studies on cost effectiveness; 

provides technical support for vaccine procurement, distribution and delivery 

U.S. Agency for 

International 

Development (USAID) 

Supports preclinical testing in animal models, development of candidate vaccine 

products, clinical testing of vaccines, operations and applied research to strengthen 

immunization programs and logistics, prepare for the introduction of new vaccines; and 

provides global expertise in demand forecasting, supply and procurement, and 

distribution and delivery to developing countries 

10 
 

III. Current Investments and Activities 

for the Development of Vaccines 

HIV/AIDS Vaccine Development Efforts 

More than 25 years after the discovery of HIV/AIDS, the pandemic continues to spread, especially in 

developing countries. HIV infection rates continue to rise in many developing countries; an estimated 2.7 

million new infections occur every year, and no cure is available. Infected persons worldwide number 

nearly 33 million, and in sub-Saharan Africa, almost 60% of infected individuals are women. 

No single approach to HIV/AIDS prevention is likely to have a dramatic impact if applied in isolation. 

Integrated approaches to prevention, detection, and management that are tailored to specific populations 

yield the best results. Unfortunately, current strategies for preventing HIV infection, including delay of 

sexual debut, partner reduction, and use of condoms are often not possible for many women in developing 

countries. Therefore, novel technologies to prevent new HIV infections are needed to complement 

currently available methods of HIV protection. All existing and developing HIV/AIDS prevention 

approaches must be tailored to best serve specific at-risk populations. 

Adding a globally effective HIV vaccine to a comprehensive prevention strategy is a crucial step to 

control the HIV/AIDS pandemic. The search for a product has been challenging. In efficacy studies, two 

vaccine candidates have not shown they protect against HIV infection or moderate subsequent HIV 

disease. As announced in September 2009, a third vaccine studied for efficacy in Thailand on 16,402 

participants has reported efficacy of 31% in an historic, first-time result proving a concept that is sure to 

lead to improved vaccine candidates. A fourth vaccine entered advanced clinical evaluation in June 2009. 

Scientific advances in defining how the human immune system attempts to protect itself against HIV are 

unfolding. The earliest events in natural infection, particularly in those who show an immune capacity to 

resist the virus, are beginning to inform new vaccine design; translating these events into a candidate 

vaccine hold great promise to have an impact on the epidemic with an eventually licensable vaccine. 

USG HIV Vaccine Development Programs 

Department of Health and Human Services, National Institutes of Health 

The discovery and development of a safe and efficacious vaccine to prevent HIV/AIDS worldwide is a 

high priority area of research for the USG. Within the U.S. Government, the NIH, through both 

intramural and extramural research programs at several institutes and centers, supports basic research, 

preclinical testing in animal models, development of candidate vaccine products, and clinical testing of 

HIV/AIDS vaccines. HIV/AIDS research budgeting and planning throughout NIH is coordinated through 

the Office of AIDS Research, part of the Office of the NIH Director, which annually reviews and 

establishes NIH-wide scientific priorities and identifies research objectives and strategies to accomplish 

these goals and priorities through an annual Trans-NIH Plan for HIV-Related Research 

(http://www.oar.nih.gov/strategicplan/). 

Within the NIH, NIAID has the lead on HIV/AIDS vaccine research, and other institutes and centers 

contribute to this effort by providing access to non-human primates for testing vaccine concepts (National 

Center for Research Resources mainly through the National Primate Research Centers); conducting 

intramural research on vaccine designs, model development and therapeutic vaccine concepts (National 

Cancer Institute); supporting trials in children and adolescents (Eunice Kennedy Shriver National Institute 

of Child Health and Human Development); and a small, focused extramural effort on mucosal vaccine 

approaches (National Institute of Dental and Craniofacial Research). 

Through its intramural program in the Vaccine Branch, and in the AIDS and Cancer Virus Program, the 

National Cancer Institute (NCI) supports AIDS vaccine development efforts through research aimed at an 

11 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

improved understanding of the pathogenesis of HIV infection, especially the early events involved in 

establishing infection, through the development and evaluation of novel vaccine approaches and 

candidates, development of improved non-human primate models for AIDS vaccine evaluation, and 

through providing unique reagents and analytical capabilities to support the AIDS vaccine research 

community as a whole. 

The Vaccine Branch in NCI’s Center for Cancer Research has several promising AIDS vaccine strategies 

under development. In a Cooperative Research and Development Agreement (CRADA) with Sanofi, NCI 

scientists played a key role in the development of the recombinant ALVAC vaccine that was the first to 

show clinical efficacy in a phase III trial in Thailand. Based on this discovery, the NCI holds a patent on 

this technology. Additionally, the NCI has a replication-competent recombinant adenovirus vaccine that 

has shown dramatic efficacy in non-human primates and is being prepared for clinical trials. NCI 

scientists have developed optimized DNA vaccines that can protect non-human primates against SIV as a 

single agent – the first evidence of such efficacy for a DNA vaccine – and that can provide therapeutic 

benefit to infected animals when given during anti-retroviral therapy. 

Furthermore, NCI researchers have developed a mucosal vaccine strategy that induces mucosal T cells 

that can have an impact on the initial transmission of the virus, and that induces both innate and adaptive 

protective mucosal immunity against SIV in non-human primates. The NCI has also pioneered work on 

the use of cytokines such as interleukin-12 and interleukin-15 as vaccine adjuvants to improve the quality 

as well as the quantity of T lymphocyte response, and has developed ways to block inhibitory effects that 

restrain the immune response to vaccines. NCI scientists are also developing other novel vaccine vectors 

and ways to utilize non-neutralizing antibodies in protection. In addition, NCI has formed a consortium 

with the Institute of Human Virology, University of Maryland, to develop vaccines based on a new 

recombinant HIV envelope fusion protein that induces broadly neutralizing antibodies coupled with some 

NCI strategies to induce T cell immunity and to enhance antibody responses. Some of these vaccine 

strategies are now being developed as combinations for greater efficacy for both prophylactic and 

therapeutic use. 

And finally, in 2009, the NCI issued an RFA initiative for the development of vaccines against HIVassociated malignancies or HIV infection. Progress to date in the understanding of the molecular 

mechanisms of AIDS and HIV infection and the development and application of treatments such as the 

widespread use of highly active antiviral therapy (HAART) in the developed world has led to greatly 

improved patient survival. However, accompanying this increased survival has been an increase in the 

incidence of HIV-associated cancers among long-term AIDS survivors. Malignancies are becoming the 

most frequent cause of death in HIV-infected populations. Given both the need for vaccines and the 

paucity of ongoing research efforts directed at vaccine development targeting HIV-associated 

malignancies, this initiative is designed to stimulate early exploratory research efforts in either 

preventative or therapeutic vaccine development for infectious causes of cancer (Kaposi’s sarcoma; 

Epstein Barr Virus, hepatitis C, Merkle Cell Polyomavirus, and human papilloma virus of the types not 

present in the current vaccine) or HIV to prevent or limit infection in the host. This initiative covers the 

breadth of vaccine development from basic science studies, through animal model development, to 

preclinical studies. However, it does not support clinical trials. The outcomes of this new research on 

vaccine development for HIV-associated malignancies and HIV will help inform NCI’s future research 

efforts in this area. 

Because the first efficacy trials did not identify an effective vaccine, the identification of new vaccine 

concepts and development of potential leads for further evaluation are urgently needed. Basic research in 

the fields of HIV natural history, pathogenesis, immunology, virology, viral and host genetics, and animal 

model development can lead to novel discoveries that can form the basis for promising vaccine 

approaches. Through concerted efforts, basic discovery research can remove fundamental obstacles to 

achieving this goal by focusing intensively on fostering new cross- and inter-disciplinary collaborations, 

and sharing of the resulting knowledge may be critical to HIV vaccine discovery. 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

In March 2008, NIAID sponsored a summit on HIV vaccine research and development. The result of this 

meeting was a consensus that an increased emphasis on basic vaccine discovery research was needed. 

Toward this end, NIAID established a new branch within the Division of AIDS’ Vaccine Research 

Program to focus on acceleration of discovery efforts, and new initiatives to support HIV vaccine 

discovery were developed. 

Scientific advances in defining how the human immune system attempts to protect itself against HIV 

continue to unfold. The earliest events in natural infection, particularly in those that show an immune 

capacity to resist the virus, are beginning to inform new vaccine design, and the translation of these 

events into a candidate vaccine holds great promise. The top priority of NIH HIV vaccine research is to 

accelerate basic research that will lead to new vaccine concepts that induce neutralizing or other broadly 

protecting antibodies, consistent and high levels of effector and memory cytotoxic T lymphocytes, and/or 

strong mucosal immune responses. As of spring 2009, NIAID had supported a total of 111 vaccine trials 

(102 Phase I, Ib, I/IIa or I/II, 4 Phase II, 2 Phase IIa, 2 Phase IIb, 1 Phase III) involving 67 different 

products and 18 adjuvants. 

NIH and other government agencies that conduct and support HIV vaccine research coordinate their 

efforts in several ways, including with: (1) the Partnership for AIDS Vaccine Evaluation (PAVE), a 

consortium of USG entities, led by NIAID and other USG-funded organizations involved in development 

and evaluation of HIV/AIDS preventive vaccines and the conduct of HIV vaccine clinical trials; (2) 

WHO-UNAIDS Vaccine Advisory Committee; and (3) the Global HIV Vaccine Enterprise, a consortium 

of independent organizations committed to accelerating the development of an HIV vaccine (see Section 

V). 

In addition, the NIAID-supported HIV Vaccine Trials Network (HVTN) modified its scientific agenda to 

increase its emphasis on small trials to address fundamental scientific questions. The HVTN, funded by 

NIAID through a cooperative agreement, conducts the majority of NIH extramural vaccine trials. The 

mission of the HVTN is to enhance the discovery and drive the development of a safe and globally 

effective vaccine for the prevention of HIV through well-designed clinical research trials that objectively 

address the critical questions of the field. The three leadership groups (core/operational, laboratory and 

statistical) are located in Seattle at the Fred Hutchinson Cancer Research Center, and the sites in the 

network, also funded by NIAID, are located in the United States and abroad. 

NIAID also solicits input from expert vaccine researchers and advocates who comprise the AIDS Vaccine 

Research Subcommittee (AVRS) of the AIDS Research Advisory Committee. Specifically, the AVRS 

assists NIAID in developing a comprehensive research program aimed at expediting the discovery and 

development of an effective HIV/AIDS vaccine. Additional information on NIAID’s vaccine research can 

be found at: www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/ and www.vrc.nih.gov. 

PAVE is a voluntary consortium of USG agencies and USG-funded organizations involved in HIV 

vaccine research. It was formed in 2003 with the recognition that no single entity or institution is likely to 

succeed alone in the goal to develop a safe and effective HIV vaccine. In addition to NIAID, members of 

PAVE include OAR, the NIAID-funded HVTN, USAID, MHRP, CDC, and IAVI. NIAID plays a key 

leadership role in PAVE by providing the chair for the partnership and operational support. 

The Global HIV Vaccine Enterprise (Enterprise) was initially proposed in 2003 by prominent HIV/AIDS 

researchers, public health officials, and advocates, and endorsed by the leaders of the G-8 nations in June 

2004. The Enterprise is a “virtual” consortium of independent organizations committed to accelerating the 

development of a safe and effective preventive vaccine for HIV/AIDS through the creation and 

implementation of a shared strategic scientific plan, mobilization of resources, and greater coordination 

and collaboration among HIV vaccine researchers worldwide. 

The Vaccine Research Center (VRC) was conceived in response to the growing epidemic of HIV/AIDS. 

Despite more than 15 years of research, efforts to develop an effective HIV vaccine were unable to 

13 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

deliver an effective vaccine, and it was proposed that a dedicated research center composed of 

investigators working on different aspects of this problem would be better able to address this challenge. 

The primary focus of activities at the VRC is the development of an effective HIV/AIDS vaccine. Using 

gene-based vaccine platforms, such as DNA plasmids and recombinant adenoviral vectors, VRC 

investigators have developed and tested numerous vaccine products and have advanced the most 

promising candidates into clinical testing. In the process of addressing the need for an HIV/AIDS vaccine, 

innovative technologies (e.g., DNA vaccines, novel viral vectors, structure-designed proteins) have been 

developed (http://www3.niaid.nih.gov/about/organization/vrc/). 

The VRC has engaged the private sector and created multiple collaborative research and development 

agreements with large and small research and biotechnology organizations. These collaborations have 

resulted in the development of novel adenoviral vector vaccines against HIV and Ebola. VRC 

collaborations with the pharmaceutical sector have been implemented to examine the use of adjuvants in 

reducing vaccine dose requirements and to evaluate different prime-boost regimens for administration of 

HIV vaccines. In addition to basic research collaborations, partnerships with industrial organizations have 

expanded in recent years to include the manufacturing and process development activities associated with 

vaccine development. 

Also, Office of AIDS Research annually solicits input for the Trans-NIH Plan for HIV-Related Research 

from an AIDS Vaccine Coordinating committee, comprised of representatives of NIH institutes and 

centers, NIH-funded investigators, other USG entities conducting AIDS-related research, pharmaceutical 

and biotechnology groups, nongovernmental organizations, and community representatives. 

Department of Defense 

In 1985, the U.S. military recognized the emerging HIV-1 epidemic as a new threat to U.S. and allied 

forces worldwide. A military directive emerged to develop effective preventive measures to include 

prevention education, vaccine development, and implementation of novel antiviral therapies and clinical 

management tools for the DoD. The U.S. Congress mandated the formation of a U.S. Army-led 

HIV/AIDS research unit in 1986. Initially organized around a reference laboratory at the Division of 

Retrovirology at the WRAIR in Rockville, MD, the program quickly grew with affiliated research sites in 

Kenya, Tanzania, Uganda, Nigeria, and Thailand and collaborative efforts with a wide variety of national 

and international research groups. The collective program is known as the U.S. Military HIV Research 

Program (MHRP). 

The MHRP has since become an important partner in international efforts to combat this devastating 

disease. From its inception, MHRP has focused on both HIV variants that circulate in the developed 

(subtype B) and developing (non-subtype B) world given its dual mission to develop a preventive HIV 

vaccine for U.S. military personnel and for the global community. This global focus and an emphasis on 

capacity building and sustainable partnerships in Africa and Asia made MHRP unique in the early years 

of the HIV pandemic. 

Funding for the MHRP technical base of the program is provided in approximately equal proportions 

from the Military Infectious Disease Research Program (MIDRP) via DoD Research and Engineering 

programs and from external grants from NIAID. The Defense Health Program supports an extensive HIV 

diagnostics and therapeutic monitoring activity at MHRP inclusive of HIV testing, HIV viral load and 

resistance genotyping capability, and infectious pathogen confirmatory testing for the Army Blood 

Program. MHRP is supported by smaller research funding from the BMGF, the Infectious Disease 

Clinical Research Program at the Uniformed Services University, and other entities. MHRP also executes 

a large prevention, care, and treatment program in Africa funded by the U.S. President’s Emergency Plan 

for AIDS Relief (PEPFAR), Department of State. 

MHRP research efforts encompass threat assessment and epidemiology, HIV diagnostics, vaccine 

development and testing, and therapeutics research. Epidemiologic studies inform vaccine development 

through the identification of at-risk populations and the enumeration of HIV prevalence, risk factors, and 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

incidence data that provide the key information to design clinical efficacy trials. Epidemiologic studies 

also provide the platform for community engagement and preparation for subsequent intervention studies 

for both vaccine and therapeutic research. Parallel molecular epidemiology studies have identified the 

precise molecular structure of circulating HIV variants in MHRP focus countries. East African sites are 

predominately representative of subtypes A, C, D, and intersubtype recombinants thereof. Nigeria is a 

mixture of CRF02_AG and G infections, while Thailand represents CRF01_AE and B. Together, MHRP 

research stations are well-positioned to test the concept of global protection of prospective HIV vaccine 

candidates. 

While the MHRP’s primary focus is on developing a globally effective preventive HIV-1 vaccine, the 

program provides effective prevention, care, and treatment programs in each of the communities in which 

research is conducted in order to provide an ethical, non-coercive environment to conduct clinical 

research. This aspect of the program is funded by PEPFAR and engages both civilian and military 

populations in sub-Saharan Africa. The research and PEPFAR programs exist in the same locations. This 

provides a vibrant synergy among clinical capabilities, enhanced public health infrastructure, and clinical 

research. The provision of these services makes MHRP a trusted member of the community and develops 

human capacity for both HIV and non-HIV programs. MHRP PEPFAR programs have developed incountry relationships with CDC, USAID, DoD, Peace Corps, and other stakeholders and has built 

powerful partnerships with host country civil society, government, academia, and nongovernmental 

organizations. 

Funding of MHRP’s technology base is a mixture of intramural Army and extramural NIAID funds. The 

latter are a blend of a Y01 (interagency agreement; multi-project/core grant) that funds HIV vaccine 

preclinical and clinical research; clinical research funds from the Division of Clinical Research managed 

by the Infectious Disease Clinical Research Program supporting therapeutics and Ebola-Marburg vaccine 

research; funding of a clinical trials unit of the AIDS Clinical Trials Group (ACTG) headquartered in 

Rockville, MD, with clinical research sites in Kericho and Eldoret, Kenya. Recent direction from the 

NIAID and ACTG has enabled MHRP to begin to explore HIV-malaria interactive research initiatives in 

Kenya. 

MHRP preclinical research is heavily based on quality humoral and cellular immune assessment 

laboratories capable of state-of-the-art B and T cell epitope mapping, neutralization assays (PBMC and 

TZM-bl), ELISPOT, intracellular cytokine staining, chromium release CTL, and multiparameter flow 

cytometry. Program scientists are engaged in novel antigen discovery, liposomal formulations, and 

investigation of polyspecific monoclonal antibodies simultaneously binding to lipid and protein epitopes, 

and dissection of dendritic cell function. A vibrant host genetics group is discovering novel genetic 

associations with HIV acquisition, disease progression, immune response, and vaccine efficacy using 

gene-directed and (via collaboration) genome wide association studies. Onsite capabilities in 

transcriptional profiling and transcriptional control analysis complement the host genetics approach by 

providing the basis for mechanistic distillation of associative discovery. Extensive capabilities for HIV 

molecular epidemiology complete the molecular biology discovery group. 

The Defense Health Program funds MHRP to maintain key clinical care support to U.S.-based military 

hospitals and to the Department of the Army. MHRP provides technical oversight of all Army HIV 

testing (1 million tests/year) and executes 100,000 tests yearly in a College of American Pathologists 

(CAP) certified laboratory. All HIV viral load and resistance genotyping tests and all confirmatory 

transfusion transmissible testing for Army Blood Program donations are performed on site. MHRP 

provides clinical laboratory oversight to CAP certified laboratories in Kenya, Tanzania, Uganda, and 

Thailand. 

MHRP has conducted a Phase III trial of a canarypox prime, gp120 protein subunit boost strategy in 

16,402 HIV seronegative, volunteers in Thailand. This study passed interim analysis and futility analysis 

over the past two summers. The study closed for analysis June 30, 2009. Major trial results announced 

15 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

worldwide on September 24, 2009, reported that the investigational HIV vaccine regimen was safe and 

modestly effective in preventing HIV infection. According to final results released by the trial sponsor, 

the U.S. Army Surgeon General, the prime boost combination of ALVAC HIV and AIDSVAX BE 

lowered the rate of HIV infection by 31.2% compared with placebo. In the final analysis, 74 placebo 

recipients became infected with HIV compared to 51 in the vaccine regimen arm. The efficacy result is 

statistically significant. The vaccine regimen had no effect on the amount of virus in the blood of 

volunteers who became HIV-infected during the study. 

These findings have important implications for the design of future HIV vaccines and how they are tested; 

however, additional research is needed to better understand how this vaccine regimen reduced the risk of 

HIV infection. Given the significant threat of HIV infection worldwide, an efficacious vaccine is urgently 

needed as part of a broader prevention effort to help control the epidemic. 

Collaborating partners on this study, referred to as RV144, include the U.S. Army, the Thai Ministry of 

Public Health, NIAID, NIH, Sanofi Pasteur, and Global Solutions for Infectious Diseases. The 

collaborators are already working with external experts to determine the need for additional studies on 

this vaccine regimen and consider the impact of this study’s findings on other HIV vaccine candidates. 

U.S. Agency for International Development 

Since 2001, USAID has funded, through PEPFAR, the International AIDS Vaccine Initiative (IAVI), a 

U.S.-based, nonprofit organization that acts as a virtual pharmaceutical company to accelerate the 

development and clinical testing of HIV vaccine candidates. IAVI and its network of partners research 

and develop vaccine candidates. USAID funding accelerates the development and introduction of new 

vaccine candidates and technologies and helps link vaccine designers with manufacturers and developingcountry sites suitable for testing promising HIV vaccine candidates. Through IAVI, USAID supports 

biomedical research in all phases of HIV vaccine clinical R&D and other work to pave the way for 

introducing a vaccine when it becomes available. For IAVI’s part, its R&D is focused on developing and 

evaluating novel vectors and vaccine designs, and testing them in nonhuman and human trials while 

preparing communities, so they can understand the wide variety of HIV vaccine trial results. 

Specifically, USAID support for IAVI encompasses: 

Designing and implementing preclinical and clinical studies of vaccine candidates 

Supporting IAVI’s core immunology laboratory and primate facilities 

Building local capacity at trial sites 

IAVI’s scientists are particularly focused on a few essential areas of viral behavior to inform and 

accelerate vaccine discovery. Among the most important efforts are the need to develop more reliable 

animal models that may be more predictive of HIV pathology and resistance in humans; to understand 

early events in HIV infection; to understand the behavior of HIV and how it does irreversible damage to 

the host, and how host genetic profiles affect HIV acquisition and disease progression; to discover how 

protection can be mobilized to the infection site while defining the structures on the HIV envelope that 

are the targets of broadly neutralizing antibodies; to design a vaccine ultimately capable of inducing 

antibodies that can be effective against many strains of HIV; and to optimize laboratory techniques 

capable of more accurately and quickly measuring responses to HIV candidate vaccines – particularly in 

resource-poor areas. 

IAVI invests the bulk of its resources in the research and clinical assessment of candidate vaccines against 

strains of HIV that are prevalent in the developing world where some 95% of new HIV infections occur. 

Their scientific team works with more than 40 academic, commercial and government institutions to 

develop and assess candidate HIV vaccines. Together with their partners, IAVI has evaluated eight 

vaccines in 26 early-stage clinical trials conducted in 11 countries across four continents. To do this 

critical work, they, along with local research institutions, have developed a network of sophisticated 

16 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

laboratories in India and in southern and eastern Africa. Their Human Immunobiology Laboratory in 

London helps coordinate the work of these laboratories and assures quality across the network. 

In the arena of vaccine design, IAVI has brought leading HIV researchers together into three scientific 

consortia: the Neutralizing Antibody Consortium; the HIV Live-Attenuated Consortium; and the Vectors 

Consortium, all of which address the key obstacles to the development of an effective HIV vaccine. In 

developing countries, IAVI works closely with governmental, community, and civic organizations to 

ensure the transparent and ethical conduct of clinical trials. They support the staffing and training of 

community advisory boards representative of the communities in which clinical trials are conducted. 

IAVI assists in educating people about vaccine trials and the need for HIV vaccines, and helps to build 

both the clinical and scientific capacity required to run a long-term program of vaccine trials. They also 

analyze, develop, and advocate policies to promote the involvement of the private sector in HIV vaccine 

research and development, and polices that will ensure that once an HIV vaccine is developed, it will be 

swiftly produced, distributed, and made affordable worldwide. 

Inherent in this public-private partnership, are collaborations among university, government, and privatesector groups to ensure that the appropriate resources are available for each phase of product 

development. Private sector investment historically brings most vaccines to market, but their 

contributions are less than 15% of the total investment in HIV/AIDS vaccine (see Figures 2 and 3, 

below). USAID’s partnership with IAVI promotes policies to strengthen the involvement of the private 

sector in HIV vaccine R&D. 

USAID actively collaborates with the NIH, the CDC, and the MHRP through the PAVE, as described 

above by the NIH. 

Figure 2 

17 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Figure 3 

Source: http://www.hivresourcetracking.org/treatments/vaccines 

Future Direction of USG HIV Vaccine Development 

Department of Health and Human Services/National Institutes of Health 

It bears repeating that HIV vaccine clinical research remains a high priority at the NIH and that the NIH 

will continue to support vaccine research through investigator-initiated grants as well as solicited research 

programs. The Fogarty International Center will continue supporting extensive training opportunities for 

international investigators in many prospective vaccine trial sites. 

NIAID’s active involvement with PAVE and South African AIDS Vaccine Initiative will also continue, 

increasing its ability to conduct HIV vaccine trials in developing countries and address issues and needs 

specific to a given region. NIH continues to conduct and/or support clinical trials of vaccine candidates 

through the HIV Vaccine Trials Network (HVTN) and the NIAID Dale and Betty Bumpers Vaccine 

Research Center (VRC), as well as through collaborations with the MHRP. 

NIAID is supporting a trial (HVTN 505) using the VRC vaccine candidate based on a DNA/rAd5 primeboost strategy to address specific scientific questions. HVTN 505 will evaluate whether the VRC vaccine 

can reduce viral load in vaccinated people who subsequently become HIV-1 infected due to sexual 

exposure. This trial opened to enrollment in June 2009 and is expected to have the first endpoint analysis 

in 2012; it is being conducted in the United States. The trial design has taken into consideration the 

findings of the STEP trial, a Phase IIB study of a vaccine developed by Merck. The STEP study 

efficiently determined that the vaccine candidate was not effective in preventing infection or lowering 

viral load among those who become infected but has provided important information for further vaccine 

discovery efforts and trial design. In the wake of the results from the Thai HIV vaccine trial, NIAID will 

18 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

be actively collaborating with others to garner as much information as possible from the trial data; that 

information will be used to guide and improve NIAID’s future initiatives for HIV vaccine design and 

development, and support the evaluation of improved HIV candidate vaccines 

Department of Defense 

MHRP’s vaccine development strategy before the termination of the Merck studies was based on the 

canarypox/gp120 approach and the NIH DNA/Ad5 strategy as a developmental alternative. More novel 

approaches centered on DNA prime/Modified Vaccinia Ankara (MVA) vectored products were the third 

developmental line. Post-Merck study results have caused MHRP to redirect its second and third line 

vaccine development strategies. The NIH DNA prime/Ad5 boost program has been discontinued and the 

MVA program accelerated. Heterologous vector approaches (MVA/Ad26 with Harvard University and 

MVA/Ad35 with IAVI) will be pursued. Exploratory alternatives to DNA priming such as BCG are being 

developed. MHRP has now moved from collaborative integrated non-human primate heterologous SIV 

challenge studies to clinical development planning. New animal and clinical studies are being pursued 

using DNA delivered by electroporation and mosaic inserts to raise the magnitude and breadth of the 

elicited immune response to vaccines. 

MHRP has also adjusted to the changing directions of the field by reemphasizing discovery research and 

establishing strategic partnerships with the NIAID-funded Center for HIV/AIDS Vaccine Immunology 

(CHAVI), ACTG, DoD Global Emerging Infections Surveillance and Response System, and the Army 

malaria program. One example of this direction is the development of a novel acute HIV infection study 

designed to both develop more efficient higher risk HIV cohorts and to identify individuals in the very 

earliest stages of HIV infection (prior to the humoral immune response) to synergize with CHAVI studies 

and investigate the earliest host-pathogen interactions with a view to better inform HIV vaccine 

development. This study (RV 217) is funded by both NIH and intramural Army funding. Taken together, 

the MHRP represents a broad-based, highly collaborative, and highly integrated research platform with 

strong epidemiology, preclinical, and clinical research capabilities embedded in a robust prevention, care, 

and treatment environment operating in six countries on three continents. 

The program is well positioned to pursue the development of globally effective HIV vaccines, innovative 

HIV therapeutics research, informative HIV epidemiology studies, and diagnostic studies. MHRP is 

diversifying to allow its research platforms to conduct avian influenza/pandemic influenza surveillance 

and Ebola-Marburg vaccine studies. This provides MHRP a more flexible platform for sustainable clinical 

research in the current milieu of HIV/AIDS research. MHRP’s strategic alignment following the results of 

the Merck vaccine studies have allowed the program to fully maintain its discovery and clinical research 

capabilities worldwide and have provided the underpinning of a more novel and value added research 

approach with its counterpart HIV research partners in the field. 

U.S. Agency for International Development 

USAID support for IAVI has helped to advance and accelerate HIV vaccine research and development, 

leading to important discoveries and new directions for the field. Recent HIV vaccine research findings 

are providing new hope in the search for model antibodies like those of people whose immunity provides 

effective viral control. These special antibodies known to neutralize, or lock-up the virus will inform 

scientists on exactly what the structures in a vaccine must look like and how they must function, in order 

to develop similar structures employing man-made biological techniques. This new body of work is 

evolving rapidly, and USAID’s support of IAVI is key to its progress. 

In the coming year, through its cooperative agreement with IAVI, USAID hopes to accelerate the search 

for safe and effective products that can prevent HIV infection. Among the expectations are IAVI’s 

continued efforts to identify naturally occurring antibodies capable of neutralizing a wide variety of HIV. 

This promising work relies on activities that USAID supports IAVI to conduct in developing countries. 

Samples from otherwise healthy, HIV-positive volunteers are collected from IAVI’s global vaccine 

19 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

testing sites and assessed to identify broadly neutralizing antibodies that are already providing invaluable 

clues in developing a vaccine. 

Other USAID priorities include rapidly advancing small-scale efficacy trials, called Screening Test of 

Concept (STOC) trials, of those HIV vaccine candidates in the current pipeline that will have already 

exhibited safety in preclinical and Phase I clinical and immunogenicity studies. STOC trials depend on 

the monitoring of HIV viral load subsequent to infection in the absence of antiretroviral therapy. This trial 

design may be challenged by the use of antiretroviral therapy in individuals at high risk for acquiring HIV 

infection if results of current studies show efficacy, as these populations may then be placed on 

antiretroviral therapy. Next generation candidates that target mucosal immunity and vectors that infect 

persistently are two other promising new directions that IAVI is pursuing. 

This work is supported by ongoing vaccine preparedness activities to ensure that clinical trials proceed 

ethically and in a manner responsive to the needs of volunteers and their communities. IAVI will conduct 

gender sensitivity trainings for staff at collaborating research centers and implement recommendations 

from their ongoing study of gender-related barriers to participation in HIV vaccine clinical trials. 

Policy research priorities for the coming year will focus on making the business and investment case for 

HIV vaccines and promoting policies to encourage greater participation by the public and private sectors 

in research and development. Additional information can be found at: International AIDS Vaccine 

Initiative (publicpolicy@iavi.org). 

Tuberculosis Vaccine Development Efforts 

Tuberculosis (TB) is a global health emergency that kills approximately 1.7 million people each year, the 

majority of whom are socio-economically disadvantaged or already marginalized in society. In addition to 

persons with active pulmonary TB, the form of the disease primarily responsible for spreading the TB 

pathogen, Mycobacterium tuberculosis (Mtb), over one-third of the world’s population is thought to carry 

latent, asymptomatic infection. While TB can be found across the globe, the majority of cases (~80%) are 

clustered in 22 developing countries. TB was considered “managed” after the advent of chemotherapy in 

the mid-1900s and widespread vaccination after the introduction of the TB vaccine Bacille Calmette 

Guerin (BCG) in the 1920s. While it is provided as an almost universal neonatal vaccine in TB-endemic 

countries through the WHO’s Expanded Program on Immunization, BCG is not sufficient to provide 

protection against pulmonary TB in children or adults; it does provide limited protection against 

disseminated TB in infants and young children. 

The 1980s saw a rapid increase in the number of TB cases, and control programs, guided by the WHO, 

were established to better track and care for TB patients. In 2007, an estimated 9.27 million new cases 

occurred, which represents a global average of 139 cases per 100,000 population. Initial gains in TB 

control were reversed with the appearance of HIV/AIDS, and today, TB is the leading cause of death for 

people with HIV/AIDS. Of the 1.7 million annual TB deaths, approximately 456,000 are among persons 

who were HIV positive. HIV-positive persons are 20 times more likely to develop TB than are HIVnegative persons, and HIV infection is the most significant risk factor for a latent Mtb infection to convert 

to active TB. 

In 2000, the global health community launched the Stop TB Partnership, sponsored by the WHO, to 

coordinate and inspire support for global TB control. The Stop TB Partnership has taken leadership of the 

global fight against TB, and the USG is a prominent member of the partnership. The first Global Plan 

2001–2005 catalyzed governments and donors to address the issue of TB in their countries and 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

established key global targets for detection and treatment of active TB through Directly Observed 

Treatment, Short Course (DOTS)5

 programs. 

This plan also recognized the need for biomedical research in TB as an integral part of a global strategy 

with the expectation that further research will modernize health care interventions and create new tools to 

fight the epidemic. Building on the success of the first Global Plan, the Stop TB Partnership launched the 

Actions For Life – The Global Plan to Stop TB 2006–2015, which references the Millennium 

Development Goal of halting and beginning to reverse the incidence of TB by 2015, as well as the more 

ambitious Stop TB Partnership targets of reducing TB prevalence and deaths by 50% by 2015, relative to 

the 1990 baseline. The Global Plan 2006–2015 notes that “introduction of new effective TB vaccines will 

be an essential component of any strategy to eliminate tuberculosis by 2050. New TB vaccines to prevent 

childhood and adult forms of TB, to reduce TB in people co-infected with HIV, and to shorten drug 

treatment regimens will fundamentally alter our approach to TB control.” 

The Current Need for TB Vaccine Development for the Developing World 

According to WHO, it is unlikely that the global targets to halve TB prevalence and deaths will be 

achieved by 2015. This is mainly due to insufficient resources for scale-up of the Stop TB strategy, which 

remains focused on case detection and treatment of patients with already active disease, and the lack of 

new health care interventions that would transform care and reverse the trajectory of this epidemic. 

Despite active coordination around improvement of control practices through diagnosis and 

chemotherapy, the WHO has only recently recognized that novel vaccines against adult pulmonary TB 

will be needed to augment and supplement the current TB elimination strategies that are based on 

identification and treatment of persons with active TB. A mathematical modeling study published in the 

August 3, 2009, Proceedings of the National Academy of Sciences found that new tools, including 

vaccines, could significantly reduce TB incidence by 2050. The study concluded that neonatal vaccination 

with a new vaccine could decrease TB incidence by 39% to 52% by 2050. The same study found that the 

combination of a new vaccine, drug regimen, and diagnostics would decrease TB incidence by 71%. As 

such, vaccines would play an integral role in a comprehensive TB prevention and control strategy. 

(http://www.pnas.org/content/106/33/13980.abstract, accessed August 27, 2009) 

The need for an effective vaccine is also underscored by the recognition that inadequate investments in 

public health infrastructure and human resources, insufficient political commitment and resources for TB 

control programs to assure timely diagnosis and an uninterrupted, high quality supply of drugs, and 

insufficient donor funding to sustain the current resource intensive care programs are key factors slowing 

progress. The growing extent of the HIV/TB co-epidemics, which necessitates use of complicated, poorly 

tolerated and often non-compatible multi-drug regimens, and the increase of multi-drug and extensivelydrug resistant TB, which further complicates treatment regimens, underscores the critical need for 

vaccines to prevent and control the emergence of all forms of TB. New, effective vaccines would also 

relieve the burden on already stressed healthcare systems by reducing the need for input-intensive 

diagnosis and directly observed therapy. 

State of the Science and TB Vaccine Development 

There are several strategies being pursued worldwide to develop new vaccine candidates and approaches 

for TB. 

1. Recombinant BCG 

Neonatal BCG vaccine is accepted as providing good protection against pediatric forms of TB, 

disseminated TB, and TB meningitis. It does not, however, reduce the burden of adult pulmonary 

5

 Directly Observed Treatment, Short Course (DOTS) consists of five components: political commitment with increased and 

sustained funding; case detection through quality-assured bacteriology; standardized treatment with supervision and patient 

support; an effective drug supply and management system; and a monitoring and evaluation system, including impact 

measurement. 

21 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

TB; BCG vaccine is still the most frequently administered vaccine worldwide. Furthermore, BCG 

also provides moderate protection against another highly stigmatized mycobacterial disease, 

leprosy, which is prevalent in many TB-endemic countries. 

New recombinant BCG vaccines are intended to either improve neonatal vaccination to produce 

protection against pulmonary TB later in life, or to improve BCG as a priming vaccine for later 

boosting with protein, DNA or other types of vaccines. Current approaches to alter BCG include: 

(1) over-expression of Mtb antigens; (2) introduction of genes modifying the way the BCG 

interacts with the host; (3) alternation of the BCG genome to attenuate growth of the strain; or (4) 

combinations of the above in one vaccine. Recombinant BCG vaccine candidates have to date 

been evaluated in Phase I clinical trials. The most advanced recombinant BCG candidates have 

been developed by the Max Plack Institute in Germany and have entered Phase I dose-escalation 

studies. 

While recombinant BCG constructs may be an important component of novel vaccination 

strategy, these vaccines nevertheless will be required to provide tangible benefits over BCG for 

infants to complete Phase III clinical trials and licensure and to justify replacement of the current 

vaccine. These facts, combined with limited data on the incidence of pediatric TB, the lack of 

specific and sensitive tests to diagnose pediatric extrapulmonary TB, and limited data from 

randomized controlled trials to document the effect of BCG on pediatric TB, make it technically 

and ethically difficult to conduct placebo-controlled clinical trials for a potential BCG 

replacement vaccine. On the other hand, recent studies have shown that the risks of administering 

BCG, a live vaccine, seem to outweigh the benefits of protection for infants born HIV-infected; 

therefore, safer vaccine candidates will be needed in settings with high co-prevalence of HIV and 

TB. Recombinant BCG vaccine candidates currently in development are being designed to 

specifically address this important safety issue. 

2. Virally vectored TB vaccines 

MVA85, developed by Oxford University, is currently the most advanced virally vectored TB 

vaccine candidate and has reached Phase IIB trials. This construct is based on the expression of a 

key Mtb antigen by a viral vector (modified cowpox virus) and has been designed to boost BCG 

that has been received as part of standard vaccination programs in TB-endemic countries. Other 

virally vectored candidates include heat-inactivated adenovirus (Ad35) modified to carry 

mycobacterial DNA to express combinations of selected TB antigens within host cells. 

3. Adjuvanted subunit vaccines 

These candidates comprise proteins that are made up of fusions of Mtb antigens and are 

administered in combination with adjuvants to boost neonatal BCG later in life. The most 

advanced candidate subunit vaccine is GSK M72 (developed by Corixa/GSK with significant 

funding by NIAID for preclinical development). This vaccine is currently in early-stage Phase II 

clinical testing. 

4. DNA vaccines 

Several DNA vaccine candidates have been tested preclinically in animals, but candidates with 

sufficient activity to warrant advanced preclinical development have not been discovered. 

5. Other approaches 

To expand the diversity of vaccine candidates and approaches, scientists are also evaluating the 

feasibility of attenuating Mtb through multiple gene deletions to serve as safe, immunogenic 

vaccines or platforms for advanced vaccination strategies. Furthermore, a heat inactivated 

Mycobacterium vaccae preparation, administered as a series of multiple boosting injections, has 

been studied in a Phase III trial in HIV-infected persons. Observations of reduced incidence of 

22 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

pulmonary TB in adults have been made in this study and need to be assessed as primary 

endpoints in repeat prospective, randomized controlled studies. 

Irrespective of the type of vaccination strategy proposed for TB, the scientific community faces 

significant regulatory, practical, ethical and financial hurdles that are becoming increasingly apparent now 

that new vaccine candidates are entering clinical trials for the first time. Any Phase III clinical trial to 

seek licensure for prevention of adult pulmonary TB, even as a booster vaccine in adolescents or adults, 

will have to be conducted in large cohorts in multiple TB-endemic countries and will have to follow 

volunteers for many years. Phase IV effectiveness studies will have to be conducted in collaboration with 

existing TB control programs to allow comparison of annual incidence and prevalence rates in the context 

of WHO case-reporting schemes. At this time, global investment in TB vaccine development is not 

sufficient to support large-scale, multi-center Phase II and III studies. 

USG TB Vaccine Development Programs 

The USG is the largest bilateral donor supporting the implementation of TB control programs in diseaseendemic countries and TB-related research. U.S. Government funded research and support has long been 

one of the only means by which development of vaccine candidates for TB was facilitated. NIH, through 

NIAID, is the lead agency for TB research, including vaccine-related research. As of 2008, NIAID 

remains the world’s largest funder of TB research overall with an annual budget of over US$120 million 

and is the second largest funder for TB vaccine R&D. 

23 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Figure 4 

Top 12 TB Research Funders (2007) 

U.S. National Institutes of Health $121,741,199 29.7% 

Bill & Melinda Gates Foundation $115,864,538 28.2% 

European Commission $21,455,029 5.2% 

UK Medical Research Council $12,710,433 3.1% 

Dutch Ministry of Foreign Affairs $12,187,935 3.0% 

U.S. Centers for Disease Control and 

Prevention 

$11,617,000 2.8% 

Institut Pasteur $7,996,742 1.9% 

German Federal Ministry of 

Education and Research 

$4,391,435 1.1% 

Irish Aid $4,111,435 1.0% 

UK Health Protection Agency $3,903,521 1.0% 

U.S. Agency for International 

Development 

$3,893,436 0.9% 

Statens Serum Institute $3,672,882 0.9% 

Subtotal $323,545,585 78.8% 

Disease Total $410,428,697 

Figure 5 

TB R&D Funding by Type 

Vaccines 

(Therapeutic), 

0.7% 

Diagnostics, 

8.5% 

Vaccines 

(Preventive), 

Drugs, 35.3% 20.0%

Unspecified, 

3.1% 

Basic 

Research, 

32.3% 

Source: G-FINDER Report 2008 – Neglected Diseases Research and Development: How Much Are We Really 

Spending, The George Institute for International Health 

NIAID funding for TB biomedical research has created a critical mass of qualified scientists to study all 

aspects of TB, and to contribute to the development of promising new vaccine, drug, and diagnostic 

candidates. NIAID is the primary USG stakeholder responsible for supporting TB vaccine development. 

Other USG organizations will be critical for facilitating introduction of vaccines and evaluation of field 

effectiveness and will play an important role in completing epidemiological studies to enable late-stage 

and post-licensure trials. Dutch biopharma company Crucell and the Aeras Global TB Vaccine 

24 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Foundation have started a Phase I clinical trial in Kenya of the jointly developed tuberculosis vaccine 

candidate, AERAS-402/Crucell Ad35. This study of the new tuberculosis (TB) vaccine candidate in 

Kenya will be conducted by the Walter Reed Project-Kenya (WRP) at Kombewa, near Kisumu, western 

Kenya. The main parameters of the study will be to test the safety of the candidate in healthy adults, all of 

whom have been previously vaccinated with the Bacille Calmette-Guerin vaccine and a subset of whom 

have evidence of having been exposed to TB. USG support for TB has been steadily increasing since the 

mid 1990s initially as a response to outbreaks of drug-resistant TB in HIV/AIDS communities in the 

United States but since then has paralleled the increasing recognition that TB constitutes a global health 

emergency that also affects the United States. 

While NIH/NIAID’s mission is focused on fundamental and translational biomedical research that 

includes the preclinical and early clinical evaluation of new vaccines, development of new health care 

interventions requires the stewardship and support of pharmaceutical companies. In recent years, the 

BMGF established several not-for profit organizations to facilitate development and implementation of 

new drugs, vaccines, and diagnostics that may be developed through academic, for-profit, or other not-for 

profit organizations. These organizations (the Global Alliance for TB Drug Development, the Aeras 

Global TB Vaccine Foundation, and the Foundation for Innovative New Diagnostics) have facilitated the 

transition of many product candidates and tools that were initially developed with USG funding into 

advanced-stage clinical testing. Additionally, product candidates are developed through European vaccine 

development consortia funded through the European Union (TBVac and now TBVI), by small 

biotechnology companies, and several pharmaceutical firms who also received funding through 

NIH/NIAID grants and cooperative agreements or for whom NIAID contracts provided contract research 

support to facilitate vaccine discovery and animal testing. 

Coordination among TB Vaccine Development Programs 

Coordination among the various global vaccine development agencies and private partners is 

implemented through the Stop TB Partnership’s Working Group on New Vaccines. Coordination among 

the various partners is also accomplished through continual interaction, mutual consultations, workshops, 

development of milestones, and leveraging of available resources. Since clinical vaccine candidates for 

TB have only recently emerged, additional collaboration will be needed to facilitate advanced clinical 

development and field evaluation. 

Future Direction 

NIAID plays a critical role in supporting vaccine basic research, early candidate development, and animal 

testing, while other USG partners will be critical in translating new vaccines into proper use in TBendemic countries. Research efforts will be expanded to include studies for the development of 

transmission-blocking vaccination strategies for TB outbreaks that may find application in the United 

States as well as in TB-endemic countries. To contribute effectively to TB control programs worldwide, 

strategies for combining drugs and vaccines to either enhance efficacy or shorten chemotherapy for adult 

and pediatric patients may be considered. Within the USG, TB control programs are currently being led 

by USAID (lead for international TB control) and CDC (lead for domestic TB control and provides 

critical technical assistance and operational research support internationally). Inter-agency collaboration 

is actively nurtured through the Federal TB Task Force and its International TB Working Group. 

One of the key gaps in TB vaccine development remains the availability of potent and relevant adjuvants 

and the development of non-peptide antigens (such as lipids and sugars), which are already known to play 

a role in host-pathogen interactions. To facilitate the development of advanced vaccination strategies, 

more sophisticated animal model, immune, and natural disease history protocols will need to be 

established and validated. The introduction of new TB vaccines will also require tight coordination with 

TB and HIV control programs to assure the most appropriate use of novel adult or adolescent boosting 

vaccines, as well as to inform strategies for improving neonatal TB vaccination. All current and future 

25 
 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

USG TB vaccine R&D efforts are, and will continue to be, leveraged with European and other global 

vaccine development efforts to avoid duplication and assure maximum use of limited resources. 

Malaria Vaccine Development Efforts 

Approximately half the world’s population is at risk of malaria, and nearly 1 million people die of malaria 

each year; most of these deaths occur in young children in sub-Saharan Africa. Malaria is caused by 

Plasmodium parasites, transmitted by female Anopheles mosquitoes. Although four species of parasites 

infect humans, two species, P. falciparum and P. vivax, account for about 90 percent of all human 

infections; P. falciparum is the most deadly. 

To mitigate the enormous loss of life, illness, and economic burden of malaria in the developing world, 

the U.S. Government agencies have led efforts to develop a malaria vaccine for more than four decades. 

In the mid-1960s, with the emergence and spread both of resistance to DDT among mosquitoes that 

transmit malaria and anti-malaria drug resistance of malaria parasites, the World Health Assembly 

terminated the ongoing malaria eradication program as an unsustainable effort. In response to these 

events, both USAID and the WRAIR initiated efforts to develop U.S. Food and Drug Administration 

(FDA) licensed malaria vaccines. At the same time, NIAID expanded its commitment to basic and 

strategic research on the pathogenesis of malaria, yielding new understanding and technology that fueled 

vaccine development efforts. These programs have made enormous progress, transforming the notion of a 

malaria vaccine into a working research program coordinated around many investigational vaccines at 

various stages of development. At this writing, a large multicenter trial of the malaria vaccine, candidate 

RTS S is being undertaken in Africa by the PATH Malaria Vaccine Initiative (MVI) and 

GlaxoSmithKline Biologicals (GSK). Although this clinical trial is made possible through the BMGF and 

GSK, the scientific basis and development of the vaccine is directly attributable to USG programs, 

notably that of WRAIR. This vaccine has the potential to achieve significant improvements in malaria 

morbidity and mortality if it can be successfully licensed. Phase II trials have suggested a protective 

efficacy of 30% to 40% against clinical malaria, and 50% against severe malaria. However, even this 

candidate is unlikely to be effective enough to prevent malaria entirely in an immunized population. Thus, 

next generation vaccines are badly needed. 

In recent years, there have been increasing calls for efforts to control, eliminate, and eventually eradicate 

malaria. It is widely recognized that an effective malaria vaccine would substantially accelerate these 

efforts, but it is also acknowledged that efforts to achieve these goals may require novel types of vaccines 

that target the malaria parasite in different ways from the vaccine mentioned above (e.g., by blocking 

parasite stages responsible for malaria transmission) or indeed target other species of malaria parasites 

(e.g., Plasmodium vivax) that are important outside of Africa. In 2008, NIAID published a new Strategic 

Plan for Malaria Research and the NIAID Research Agenda for Malaria. Together, these documents lay 

out future directions for research as well as specific topics that will be critical to address for malaria 

vaccines and to contribute to improved malaria control, elimination and eventual eradication. 

The Current Need for Malaria Vaccine Development for the Developing World 

The GSK vaccine RTS S/AS01b, currently the most advanced malaria vaccine candidate, has begun 

pivotal Phase III testing to gather data for submission to regulatory bodies as a part of applications for 

licensure. This multicenter Phase III evaluation is the largest vaccine trial ever conducted on the African 

continent. A recently completed Phase II field trial of this vaccine, conducted on 5- to 17-month-old 

children in endemic malarial areas in East Africa, demonstrated significant efficacy (50%) in children 

immunized with the vaccine compared to those immunized with a rabies vaccine (8% versus 16% 

developed malaria respectively) over an approximately eight-month period.6

 If the applications for 

licensure are successful, it is expected that the vaccine will be available for introduction within the next 

6 http://content.nejm.org/cgi/content/full/NEJMoa0807381v1 

26 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

four to five years. It remains to be seen whether or not these promising results will translate into a useful 

modality in malaria control programs. 

Thus, although the GSK vaccine is promising, it likely falls short of what is needed to achieve maximum 

impact on malaria morbidity and mortality. Even with an efficacy of 50%, millions of children would be 

unprotected. Furthermore, as noted above, the GSK vaccine in its current form is not expected to protect 

against P. vivax. Thus, as the GSK vaccine undergoes final pre-licensure evaluation, the USG strategy 

remains focused on the development of more effective vaccines for control programs. 

USG Malaria Vaccine Development Capacity 

Although full advantage is taken of partners in academia and industry and with nongovernmental 

organizations, much of the “hands on” work of malaria vaccine development is conducted in USGsupported laboratories, clinics, and field operations. Through its various agencies, the USG is fielding 

robust programs of basic research in malaria pathogenesis and immunology, strategic vaccine research, 

and vaccine development. 

Most of the intramural basic research is done within the Department of Health and Human Services 

(DHHS), through laboratories at NIAID and within the DoD through to laboratories associated with the 

Military Malaria Vaccine Development Program (MMVP). Key intramural laboratories include the 

NIAID Laboratory of Malaria Immunology and Vaccinology and the Laboratory of Malaria and Vector 

Research, the CDC’s Malaria Branch in the Division of Parasitic Diseases, and the WRAIR and Naval 

Medical Research Center (NMRC), which comprise the DoD MMVP. 

Although it has no laboratories or trial facilities, the USAID Malaria Vaccine Development Program 

(MVDP) is a robust element of the USG effort through its funding of and close coordination with 

partners. The mission of the MVDP is to develop vaccines for use in control programs in the developing 

world. The MVDP relies heavily on partners, in particular the Military Malaria Vaccine Development 

Program, to conduct vaccine development efforts responsive to the missions of both USAID and DoD. 

This collaboration is managed through interagency agreements between USAID and the Walter Reed 

Army Institute of Research and between USAID and the Naval Medical Research Center. 

The MVDP operates in the context of the worldwide malaria vaccine development effort, which includes 

the development of vaccines for travelers, including military personnel, as well as vaccines for residents 

of endemic malarial areas, primarily children and pregnant women. This coordinated approach takes 

advantage of the innovations made by each program to advance the goals of each individual organization. 

In addition to its partnership with the MMVP, the USAID MVDP collaborates with the Malaria Vaccine 

Initiative at PATH (MVI) through congressionally directed funds. Established in 1999 and funded 

primarily by the BMFG, MVI works to accelerate the development of malaria vaccines and to ensure their 

availability and accessibility in the developing world. As such, it is a major force multiplier of the USG 

malaria vaccine development effort. 

In addition to the intramural efforts described above, through its extramural research programs, NIAID 

maintains contracts that support basic tools for malaria vaccine R&D (e.g., genomic sequencing, 

bioinformatics, research and reference reagents), preclinical services (e.g., process development for 

vaccine manufacturing, toxicology, formulation), and clinical research and trial capacity both 

domestically and abroad as well as monitoring and data management for such trials. Through its grants 

programs, NIAID also supports basic and clinical extramural research on malaria vaccines and other 

related research. Awardees include academic institutions, research institutes, and small businesses. 

CDC has a unique and highly-valued program with a wealth of parasite species and strains available for 

culture and use in preclinical vaccine testing, an insectary with a wide variety of anopheline species that 

can be infected with these parasites, and vast experience with non-human primate models to test vaccine 

candidates. 

27 
 

 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

USG Malaria Vaccine Development Programs 

As evidenced above, the U.S. Government has robust programs that utilize both USG capacity and that of 

other entities. Although formally institutionally based, the programs are in fact intricately networked with 

each other and with external partners. These vaccine development efforts are usefully divided into two 

functional categories: those targeting travelers to malaria endemic areas, such as deployed military 

personnel, and those focusing on affected populations in the developing world, whose victims are largely 

children and pregnant women. Despite these different objectives, almost all of the advances in one 

category are relevant to the other. For example, the GSK vaccine mentioned above, which could have an 

impact on malarial burden in the developing world, grew out of a program at WRAIR intended to develop 

a vaccine for military personnel. 

The USG effort toward the development of malaria vaccines for the developing world proceeds through 

the utilization of the capacities and coordination mechanisms described above. It operates in the context 

of the worldwide malaria vaccine development effort, which consists of non–U.S. laboratories and trial 

facilities funded by the European Union and the Wellcome Trust. This coordinated approach takes 

advantage of advances made by each program to achieve the goals of all organizations. 

Figure 6 

Top 12 Malaria Research Funders (2007) 

Bill & Melinda Gates Foundation $124,464,185 26.6% 

U.S. National Institutes of Health $84,422,644 18.0% 

U.S. Department of Defense $33,126,578 7.1% 

Wellcome Trust $28,255,207 6.0% 

European Commission $21,673,026 4.6% 

UK Medical Research Council $18,594,597 4.0% 

Institut Pasteur $13,142,888 2.8% 

U.S. Agency for International 

Development 

$9,249,900 2.0% 

Australian National Health and 

Medical Research Council 

$7,692,288 1.6% 

Dutch Ministry of Foreign Affairs $5,493,975 1.2% 

Irish Aid $5,481,914 1.2% 

UK Department for International 

Development 

$4,003,611 0.9% 

Subtotal top 12 funders $355,600,814 75.9% 

Disease Total $468,449,438 

28 
 

Vector Control 

Products, 3.8% 

Drugs, 45.7% Diagnostics, 0.3% 

Unspecified, 7.2% 

24.1% 

Malaria R&D 

Funding By Type, 

Vaccines 

(Preventive), 

18.9% 

Basic Research, 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Figure 7 

Malaria R&D Funding by Type 

Source: G-FINDER Report 2008 – Neglected Diseases Research and Development: How Much Are We Really 

Spending, The George Institute for International Health 

Many avenues are available for the development of vaccines with improved efficacy; their exploitation is 

limited only by the availability of human and financial resources. The USG effort is therefore focused on 

methods that offer the most promise. The following is a summary of these approaches. 

1. Development of new vaccines based on the target molecule used in the GSK vaccine 

The fact that the GSK vaccine is efficacious, albeit at a lower level than desired provides a signal 

that the target is a valid one. Thus the development of vaccines based on the same target, but 

using alternative formulations or “platforms” is judged to be a very promising approach. The 

USAID MVDP, the MMVP, MVI, and NIAID are all working toward this goal. The effort is 

greatly facilitated by the Infectious Disease Research Institute (IDRI), a nonprofit organization 

focused on developing new adjuvants for human vaccines, with financial support from BMGF 

funding. 

2. Heterologous or “prime boost” immunization 

The use of platforms such as recombinant proteins based on malaria antigens and incorporated 

into virus-like particles is an important part of 1, above. Alternatively, recombinant viruses 

capable of expressing and delivering malaria antigens to the immune system provide an important 

approach to eliciting immune responses. Both of these approaches, however, run the risk of being 

inadequate by themselves to elicit robust immune responses to the malaria antigen if the immune 

29 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

response to the non-malaria aspects of the vaccine accelerates clearance of the vaccine in the 

human host. Such inadequacy may be averted by the use of two different formulations or 

platforms, one for the initial immunization (the prime) and another for a subsequent 

immunization (the boost), so that the immune response is focused on the malaria component. 

3. Blood stage vaccines 

Malaria disease is caused by parasites in the blood, and naturally acquired immunity is developed 

against these blood stage parasites. Vaccines that could accelerate development of this naturally 

acquired immunity could prevent disease onset. A large body of information in experimental 

systems suggests that such vaccine could be developed, and efforts continue toward this goal. 

4. Combination vaccines 

Sound reasoning suggests that a combination of more than one parasite component will be needed 

in order to develop highly efficacious malaria vaccines, and this approach is reflected in the USG 

strategy. Such vaccines may involve multiple antigens from a given stage of the parasite lifecycle, 

antigens from multiple stages of the parasite lifecycle, antigens from different parasite strains, 

and even antigens from different parasite species. 

5. New target discovery 

Although projected on a longer timeline, new malaria vaccine targets and essential genes 

identifiable through the knowledge of the malaria parasite genome may ultimately provide the 

most robust approaches to malaria vaccine development. Identification of novel targets may pave 

the way for future identification and development of subunit vaccines (including combination 

vaccines based on multiple subunits) while the technical ability to “knock out” identified essential 

genes required for parasite growth, development, or virulence may enable the development of 

attenuated parasite vaccines. 

6. Transmission blocking vaccines 

Vaccines aimed at blocking development of the parasite in the mosquito could be tremendously 

powerful tool to decrease malaria transmission and help move toward goals of elimination and 

ultimately eradication. Several promising candidate antigens have been identified. Malaria 

parasites have a complex lifecycle, including developmental stages of the parasite that are 

specialized for transmission to and development within mosquitoes. Thus, a vaccine that targets 

these stages could prevent malaria transmission from person to person, although it would not 

prevent disease in an infected individual since that phase is associated with blood-stage parasites. 

Experimental data have supported the feasibility of blocking transmission with such vaccines, and 

a number of vaccine candidates have been identified and are undergoing further research, 

development and evaluation. Linking a transmission blocking candidate antigen with candidate 

vaccine antigen(s) form other parasite stages (e.g., liver or blood stage) would provide an 

attractive combination vaccine that could give individual protection and at the same time lead to 

decreased transmission. 

7. P. vivax vaccines 

P. vivax causes substantial global morbidity, and perhaps more mortality than originally believed. 

In recognition of the importance of interventions against P. vivax malaria to global malaria 

control, NIAID has actively sought to expand the research base for P. vivax vaccines, e.g., 

through its support for sequencing of the P. vivax genome. CDC has also been a leader in P. vivax 

preclinical vaccine development. 

30 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

8. Attenuated sporozoite vaccines 

Two different attenuated whole organism approaches are being tested, one based on a precise 

dose of radiation administered to normal sporozoites and a second based on targeted disruption 

(knock-out) of key liver stage genes. These approaches appear particularly promising based on 

existing models and the overall success of attenuated live organism vaccines. 

9. Novel animal models 

Malaria vaccine development has been hampered by the absence of animal models that reliably 

support the human malaria parasites, and this shortfall is being addressed by genetic engineering 

applied to both the parasite (knocking human malaria genes into rodent malaria parasites) and the 

host (humanized mouse models). 

10. Novel adjuvant formulations 

“Subunit vaccines” are composed of malaria proteins produced from other microorganisms. 

Typically, these types of vaccines are not highly immunogenic and therefore require the addition 

of strong adjuvants to achieve the desired immune response. These novel adjuvant formulations 

may induce broad immune responses to enhance immunogenicity of the subunit vaccines 

currently under development. 

Coordination among Malaria Vaccine Development Programs 

Coordination among the various USG agencies and private partners is implemented through liaison on a 

daily basis. In addition, coordination is accomplished through ongoing interaction, annual work plans, 

development of “go/no-go” criteria for progression, etc. Within the USG, coordination is facilitated 

through the Federal Malaria Vaccine Coordinating Committee, which meets periodically on an ad hoc 

basis for general dialogue and consideration of special topics requiring attention. As needed, the 

committee invites nongovernment partners to participate. 

Future Direction 

The USG malaria vaccine development programs will continue to collaborate with organizations both 

inside and outside the U.S. Government toward the goal of discovering and validating practical vaccines 

to control malaria in the developing world. Efforts not managed by the USG will be reviewed with 

interest, and the USG strategy will be modified as new research is published. Specific new approaches 

will be evaluated, often through partnership with biotech companies with specialized expertise in novel 

technologies, and selected and added to the portfolio based on the best scientific information available. 

Current approaches will be accelerated if they are determined to be promising, or discarded if ineffective. 

The USG program will remain cognizant of the changing epidemiology of malaria and adjust accordingly 

as appropriate. Following a programmatic review commissioned by the U.S. Military Infectious Disease 

Research Program, the Institute of Medicine recommended substantial expansion of malaria vaccine 

research by DoD, due to the significant threat posed by this disease to military personnel during 

deployments to tropical areas. The Institute of Medicine pointed out in 2006 that the current capacity of 

the MIDRP Malaria Vaccine Program laboratories to carry out P. falciparum sporozoite challenge trials is 

unparalleled in the world. The rate of progress will be proportional to resources available. 

Vaccine Development for Other Infectious Diseases 

While HIV/AIDS malaria, and tuberculosis are priorities in vaccine research because of their worldwide 

prevalence and high mortality rates, the USG also aims to identify new vaccine candidates for many other 

diseases such as neglected tropical diseases, enteric diseases, and dengue fever. Investigators are working 

to produce effective vaccines that are safe for the targeted populations, including those with compromised 

immune systems. 

31 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Vaccine Development Efforts for Neglected Tropical Diseases 

Neglected tropical diseases represent the most common infections of the world’s one billion poorest 

people and include a group of chronic parasitic and bacterial infections such as hookworm infection, 

ascariasis, schistosomiasis, lymphatic filariasis, onchocerciasis, Chagas disease, leishmaniasis, and 

trachoma. Robust vaccine research studies directed at many of these serious and pervasive illnesses are 

ongoing at NIH in its intramural and extramural research programs. The great majority of these efforts are 

currently in the basic research and preclinical phases, although it is anticipated that some of these studies 

will transition into a clinical phase in coming years. 

Vaccine Development Efforts for the Prevention of Enteric Diseases 

Approximately 80% of infectious diarrhea cases among travelers are caused by bacterial agents, with 

enterotoxigenic E coli (ETEC), Campylobacter sp., and Shigella sp. infections of primary importance due 

to their frequency and debilitating effects. Viral infections cause an additional 10% of illnesses, with 

norovirus playing a primary role. While a number of travel-related illnesses have vaccines available for 

prevention of infectious diseases in deployed troops, there are no vaccines licensed by the FDA for 

prevention of diseases associated with these bacterial agents. The incidence of diarrheal illness among 

travelers and the health care savings that could be realized with the reduction in post-diarrheal chronic 

illness serve to create a viable U.S. market for enteric vaccines. 

Through the DoD’s Naval Medical Research Center and Walter Reed Army Institute of Research, as well 

as the National Institute of Allergy and Infectious Disease, the USG is focusing its efforts to develop 

preventive vaccines against Shigella sp., ETEC and Campylobacter sp. Partnering with other USG 

departments, academic institutions, industry, and private foundations, vaccines targeting Shigella sp. have 

reached Phase II testing in the past year. NMRC researchers have developed an ETEC vaccine that has 

demonstrated proof-of-concept for efficacy in a passive human challenge model and in a diarrheal disease 

non-human primate model and will likely go into human phase 1 in FY10. A Campylobacter vaccine 

based on the proven principle of capsule-conjugate vaccine has been developed and under NIH U01 

funding is being manufactured for first-in-human testing in FY11. In addition, DoD scientists are working 

to solidify a collaborative partnership with PATH and other industry partners to develop vaccines 

targeting ETEC and Shigella. PATH receives funding from the BMGF for the Enteric Vaccine Initiative, 

a project for advancing the development of safe, affordable, and effective enteric vaccines for developing 

countries. 

Vaccine Development Efforts for the Prevention of Dengue Fever 

Dengue is the most important arboviral infection in the world today. The World Health Organization 

(WHO) estimates more than 500,000 people are hospitalized with severe dengue every year and more 

than 30,000 people, mostly children, die annually. Dengue’s burden is experienced most significantly in 

resource poor countries of the tropics and subtropics. Dengue also accounts for a significant proportion of 

the systemic febrile syndromes observed in travelers returning from Southeast Asia and portions of 

Central and South America. There is currently no vaccine to prevent dengue, no antiviral medication to 

treat dengue, and vector control measures are resource intensive and are often ineffective. Developing an 

FDA-approved protective tetravalent dengue vaccine would mitigate effects of dengue in many areas of 

the world. 

Numerous academic, government, military institutions, and the pharmaceutical industry are developing 

dengue vaccine candidates; more than ten candidates are in preclinical or clinical testing. Six of these 

candidates are being co-developed by either WRAIR or NMRC investigators including three which have 

entered into human clinical trials; two are in Phase I testing, one candidate is in Phase II. In addition, 

WRAIR is exploring providing the pharmaceutical company developing the lead candidate, which will be 

entering phase III testing in the next two years, access to a mature clinical trial site developed by the U.S. 

Army in Thailand. Projected timelines for licensure of the world’s first dengue vaccine is approximately 

three to seven years. 

32 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Vaccine Development Efforts for Hantavirus vaccine 

The DoD is sponsoring the only attempt to develop an FDA-licensed vaccine for hemorrhagic fever with 

renal syndrome (HFRS). HFRS is a potentially fatal hantavirus infection transmitted to humans by 

ingestion or inhalation of secreta/excreta originating from infected rodents and has had a serious impact 

on U.S. military personnel deployed to Korea. Newly emerging hantaviruses that cause highly lethal 

hantavirus pulmonary syndrome in the Americas are also a concern. Hantavirus research performed by 

the U.S. military could result in medical countermeasures against both HFRS and hantavirus pulmonary 

syndrome. Proof-of-concept DNA vaccines against HFRS and hantavirus pulmonary syndrome have been 

produced and tested successfully in rodents, rabbits, and nonhuman primates. A phase 1 clinical trial of 

the HFRS DNA vaccine is in progress. 

Vaccine Development Efforts for Scrub Typhus Vaccine 

The DoD is providing limited support to developing a vaccine that will protect troops from scrub typhus 

on a global basis. Scrub typhus an infectious disease transmitted to humans through the bite of an 

infected, immature mite. It is most commonly found in eastern and southeastern Asia, northern Australia, 

Indonesia, and southwestern Pacific islands. No other organization in the world is trying to develop a 

globally effective, FDA-approved, preventive scrub typhus vaccine, although scrub typhus is a worsening 

problem in many parts of the world. 

Future Direction 

The USG will continue to collaborate with public-private organizations in the efforts to develop vaccines 

for infectious disease such as the neglected tropical diseases, enteric diseases, and dengue fever. The great 

majority of these efforts are currently in the basic research and preclinical phases, although it is 

anticipated that some of these will move into the clinical phase in coming years. 

33 

IV. Initiatives to Create Incentives for the Research, 

Development and Manufacturing of Vaccines 

One of the largest challenges in the development of new vaccines designed for the developing world is 

the financial risk associated with developing products for beneficiaries who may ultimately be unable to 

afford them. In order to encourage greater private-sector engagement in the research, development, and 

manufacturing of vaccines, incentives are needed to address specific barriers along the R&D to delivery 

pathway. The U.S. Government is exploring a range of incentives and innovative financing mechanisms. 

However, before increasing its commitment to these various mechanisms, further study is required to 

determine which mechanisms are best designed to share risk at critical junctures, most appropriate for 

USG investment, and are feasible. 

It often takes more than 10 years, and sometimes decades, to develop a vaccine, and many that start out as 

promising candidates never come to completion for a variety of reasons ranging from scientific barriers, 

to decisions not to further develop a vaccine based on commercial market failure. Incentives could 

address specific hurdles identified in the R&D process of a specific vaccine. However, these hurdles and 

incentives vary by vaccine and the point in the research and development pipeline one is attempting to 

influence. 

Industry operates on a “go/no go” decision framework that is revisited many times along the R&D 

pathway. They must make multiple strategic decisions about how much longer they will continue to 

invest time, money, and human resources on a particular vaccine during the development life of a 

product. Market considerations are taken into account as potential candidates move along the 

development continuum. Total investment in any product will not exceed a certain percentage of the total 

estimated market value of the product in development. Decisions around manufacturing capacity for a 

vaccine are made four-to-five years before a product becomes available on the market, and these 

decisions are based on complex market analysis. There is continuous reevaluation. Investments in supply 

capacity are determined against the size of the market for the product and the price the market will bear. If 

the global community is interested in ensuring developing countries have vaccines available to them, it is 

critical that by the time industry makes supply capacity decisions, demand forecasting for developing 

countries is well underway in partnership with industry. There are many points along the decision 

pathway where incentives could help deliver the positive outcomes for developing country benefit. 

There are a range of incentives and innovative financing mechanism that have an impact on the vaccine 

development. Broadly these mechanisms include: 

1. Basic and transnational research incentives 

2. Product development incentives 

3. Market preparation incentives 

Basic and Transnational Research Incentives 

Basic research incentives provide investment funds that can be used during the earlier stages of vaccine 

development. Primarily through NIH, the USG has programs and strategies in place to assist individual 

investigators to investigate new concepts, small groups to develop vaccine candidates to test in animal 

models, and larger consortia that can test vaccine-related concepts from basic research through clinical 

studies. 

Examples of such basic research incentive programs can be found in NIH’s HIV R&D portfolio. From 

industry’s perspective, the risk-benefit ratio for developing HIV vaccines is heavily skewed toward risk, 

largely because of the enormous scientific obstacles to developing HIV vaccines. NIH’s programs help to 

mitigate this risk by supporting HIV vaccine-related research aimed at overcoming these scientific 

35 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

obstacles at several levels. Programs and strategies are in place to assist individual investigators to 

investigate new concepts, small groups to develop vaccine candidates to test in animal models and larger 

consortia that can test vaccine-related concepts from basic research through clinical studies. 

Although basic and preclinical research is largely conducted in academic institutions, small business 

innovation research and small business technology transfer programs directly provide economic 

incentives and the engagement of small businesses in research and development that has the potential for 

commercialization (http://grants.nih.gov/grants/funding/sbirsttr_programs.htm). 

NCI and NIAID intramural investigators have had long-standing material transfer agreements and 

cooperative research and development agreements with pharmaceutical partners 

(http://www3.niaid.nih.gov/about/organization/odoffices/omo/otd/When_to_use_MTA_CRADA.htm). 

NIAID also encourages industry partnership by directly funding development, manufacturing, and/or 

testing of vaccines in collaboration with industry, providing opportunities for the private sector to 

contribute unique capabilities and intellectual property to the effort while minimizing their financial risk. 

Finally, NIH is the largest USG funder for domestic and international vaccine clinical trials and the 

supporting infrastructure that test candidate products from both small biotechnology and large 

pharmaceutical companies. 

The status and complexity of HIV/AIDS research require a multi-pronged approach to support discovery 

and development activities at all levels, from fundamental basic research to clinical research and all 

phases of clinical trials. NIH has invested significant effort and research dollars on HIV/AIDS vaccines 

since the mid-1980s and has a number of research programs that target all phases of vaccine research. 

These include: 

Center for HIV/AIDS Vaccine Immunology (CHAVI) – Established by NIAID as its main 

contribution to the Global HIV/AIDS Vaccine Enterprise, CHAVI is a “virtual” vaccine center 

comprised of 62 collaborating investigators in 26 institutions in seven countries in North 

America, Africa and Europe. CHAVI aims to overcome key immunological roadblocks in HIV 

vaccine development, with the specific goals of: 

1.	 elucidating early viral and immunological events and host genetic factors associated with 

transmission, establishment of infection, and (partial) containment of virus replication; 

2.	 determining correlates of SIV immune protection in primates; 

3.	 designing, developing, and testing novel immunogens and adjuvants that elicit persistent 

mucosal and/or systemic immune responses in humans and primates; and 

4.	 evaluating HIV-1 vaccine candidates in early phase clinical trials. CHAVI has developed 

multiple strategies for addressing these objectives, including the study of early 

immunological and virological events during infection, characterization of the first seeded 

viruses and their evolution in response to the host immune response, and the identification of 

host genetic factors associated with partial containment of virus replication. 

Additional information can be found at: http://chavi.org. 

Phased Innovation Awards – A grant program that fosters exploratory, high-risk, investigatorinitiated HIV vaccine research at the earliest stages of concept genesis and evaluation. These 

awards are open to competition from investigators at for-profit and not-for profit institutions. 

HIV Vaccine Research and Design (HIVRAD) – The goal of this grant program is to use a 

multidisciplinary approach to answer scientific questions related to HIV vaccine development. 

The program has been utilized by both academic and industry investigators to support basic 

vaccine research and design, including concept testing in animal models, mechanism of action 

studies, and studies of immune correlates. 

Integrated Preclinical/Clinical AIDS Vaccine Development – A grant program that targets 

research at the preclinical-clinical interface of the HIV vaccine research pipeline. This program 

36 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

supports consortia of experts in animal models, molecular biology, immunology, and early 

clinical trials to pursue the refinement of specific vaccine concepts. Vaccine clinical lot 

production and early human clinical studies within the period of the award are expected. This 

program has enabled several consortia to contract for vaccine development and production with 

biotechnology or pharmaceutical companies. 

HIV Vaccine Design and Development Teams – Public-private partnerships of scientists from 

industry and/or academia who have identified specific vaccine concepts amenable to accelerated 

product development. These awards are milestone-driven contracts designed to encourage rapid 

advancement into clinical studies. Twelve contracts have been awarded since 2000 under this 

mechanism, involving ten separate companies and multiple academic collaborators. 

Funding and technical support as well as selected reagents and evaluation resources are available to both 

academic and industry partners through the HIVRAD, Integrated Preclinical/Clinical AIDS Vaccine 

Development, and HIV Vaccine Design and Development Teams programs. 

The NIAID initiatives directed at support of HIV vaccine discovery include: 

Highly Innovative Tactics to Interrupt Transmission of HIV – A grant program designed to 

stimulate research on novel, unconventional, “outside the box,” high risk, high potential and high 

impact approaches that might provide long-term protection from HIV acquisition. 

Basic HIV Vaccine Discovery Research – A grant program designed to support the generation 

of new knowledge that will inform new conceptual approaches to HIV vaccine design. The 

program aims to attract scientists from the basic disciplines of immunology, virology, structural 

virology, genetics, and cell biology to work on HIV vaccine research and encourages crossdisciplinary research activities. 

B Cell Immunology Partnership for Protective HIV-1 Vaccine Discovery – A grant program 

to foster fundamental research on B cell immunology in conjunction with structure-based 

immunogen design to derive new understanding and approaches for development of HIV 

vaccines that induce neutralizing antibodies. The program will foster networking and sharing of 

knowledge, reagents and protocols to enhance all advancements in the field. 

Through multiple contracts, NIAID also provides substantial resources for all phases of preclinical 

development and evaluation of candidate HIV vaccines, including in vitro laboratory studies and in vivo 

testing in nonhuman primates. These resources are described below and can be found at 

www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/resources/. 

Reagent Resource Support Program for AIDS Vaccine Development – Produces or purchases 

reagents needed for HIV vaccine research, carries out quality control, maintains a Web-based 

reagent database, and ships reagents nationally and internationally to NIAID-supported HIV 

vaccine grantees, contractors, and others. Industry partners as well as academic investigators have 

provided reagents to this resource. 

HIV Database and Analysis Unit – Compiles and analyzes data in several areas relevant to HIV 

vaccine research. This unit, based at the Los Alamos National Laboratory in New Mexico 

consists of three related databases: an HIV Genetic Sequence Database, an HIV Molecular 

Immunology Database, and a Nonhuman Primate Vaccine Trials Database. These databases are 

publically available to any investigator conducting HIV-related research. 

Simian Vaccine Evaluation Unit (SVEU) – This contract supports the evaluation of the 

immunogenicity and efficacy of candidate HIV vaccines in the nonhuman primate model with the 

objective of gaining information that can be applied to the development of HIV vaccines for 

human use. The SVEUs conduct initial pilot studies for assessment of the immune responses 

generated in response to the immunization with a candidate vaccine. They also conduct larger 

studies that allow viral challenge of the immunized non-human primates with SIV or SHIV virus 

to evaluate the vaccines’ ability to generate immune responses that block infection, control virus 

37 
 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

replication, or slow/prevent disease progression. Studies designed by individual investigators as 

well as teams or consortia have utilized this mechanism of support for these expensive, but 

critical, studies of HIV vaccine concepts. Although pharmaceutical companies may have some 

resources for these studies, it is rare that a biotechnology company has the ability to conduct 

nonhuman primate studies without specific support through this mechanism. 

Core Immunology and Virology Contracts – These contracts carry out immunological and 

virological assessment of non-human primates under study through the SVEUs. The objective of 

the non-human primate core laboratories is to ensure standardization and comparability of the 

assays conducted for preclinical non-human primate studies and to provide a common basis for 

assessment of the immunogenicity and efficacy of candidate HIV and SIV vaccines. Several 

biotechnology groups have worked with NIAID for evaluation of their products on these 

contracts. 

Preclinical Master Contract – This contract provides a complete spectrum of support for 

investigator-initiated vaccine development including small-scale R&D, cGMP manufacture of 

investigational prophylactic HIV vaccines, preclinical safety testing, and regulatory 

documentation support leading to IND submission for Phase I-II clinical testing. It provides a 

mechanism for rapid movement from vaccine discovery phase to human clinical testing. This 

contract also allows NIAID to partner with and fund biotechnology and pharmaceutical 

companies that have the capability of producing test lots of candidate HIV vaccines. 

Product Development Incentives 

Product development incentives provide investment funds to stimulate the development of new vaccines. 

Private-public product development partnerships (PDPs) are an example of partnerships that have been 

created to make incentives available. PDPs are established to provide direct support for basic research and 

clinical trials in particular disease area. There are several PDPs of varying size and portfolios that have 

been established that relate to vaccine development and the USG has played a key role in many of them. 

Examples of PDPs that have been mentioned earlier in this report include the Malaria Vaccine Initiative, 

Malaria Vaccine Development Program, and the International AIDS Vaccine Initiative. PDPs have 

proven to be effective in accelerating the development of vaccines for developing countries. 

PDPs make strategic investments in vaccine development efforts in academia, biotechnology, and 

pharmaceutical companies to advance the most promising technologies. In return for those investments, 

the partner companies agree to pricing or supply terms that will ensure the availability of the product for 

use by public health systems in low-income countries. 

One striking example of a PDP success, where the USG (through FDA, CDC and USAID) has 

successfully partnered with BMGF, PATH and WHO, is the Meningitis Vaccine Project (MVP). The 

MVP is a partnership of PATH and the WHO that was created in 2001 as a BMGF-funded partnership 

with the goal of eliminating epidemic meningitis in sub-Saharan Africa through the development, testing, 

licensure, and widespread use of affordable conjugate meningococcal vaccines. MVP is in the final stages 

of evaluation and licensure of a conjugate vaccine that targets group meningococcal meningitis, which 

causes most epidemics of meningitis in Africa. The group A meningococcal conjugate vaccine (Men A 

conjugate vaccine) has been shown to be immunogenic and safe in completed Phase I, Phase II, and Phase 

II/III trials. An infant study is ongoing, and two Phase IV studies are planned to begin in 2009. The 

regulatory dossier will be reviewed by the Indian licensing authorities and by WHO for pre-qualification 

by the end of 2009. The FDA’s Center for Biologics Evaluation and Research laboratories provided the 

quality vaccine supplier, Serum Institute of India, a specific required technology and the requisite 

training. A European company provided the initial supply of one critical material necessary to produce the 

meningitis vaccine, while Serum Institute developed their own material. USAID provided funding to 

support the Indian regulatory agency to ensure they will be strong enough to provide oversight for this 

new vaccine, and for specific African country-level studies to gather the economic data around the 

38 
 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

epidemics of meningitis this vaccine is designed to eliminate. CDC assisted with providing the necessary 

epidemiologic analysis to determine the disease burden, and additional country-level support to 

strengthen the introduction of the vaccine. Coordination and partnership have been exemplary over the 

life of this project. USAID is providing funds for an independent evaluation of the business model in light 

of the promise it holds for potential future projects. This high quality meningitis vaccine will be available 

for less than 40 cents a dose for the African countries where these epidemics occur. Funding for the 

vaccine is still not secure, but efforts are underway to find additional funds. 

More information about PDPs appears in Section V below, “Expansion of Public-Private Partnerships and 

Leveraging Resources from Other Countries and Private Sector.” 

Market Preparation Incentives 

Market preparation investment involves the engagement of the USG and partners to lay the ground work 

for informed, sustainable introduction of vaccines into developing countries. Industry looks to the global 

community for expertise in immunization programs in developing countries. These markets represent risk 

for industry. If they invest in the supply capacity to provide vaccines for these populations, will anyone 

buy the vaccines? For how long? Are they able to safely deliver the vaccine to the intended population? 

Industry looks to the global community, including USG agencies, to provide the information necessary to 

ensure robust immunization programs exist to safely reach target populations and to provide the funding 

necessary to purchase the vaccines. If these risks are not mitigated, industry is not likely to respond to the 

needs of developing countries. 

USAID contributes market preparation expertise in: 

Building immunization programs in developing countries 

Improving vaccine logistics 

Provision of expertise in vaccine demand forecast modeling and estimates
 

Informing procurement practices 

Improvement of regulatory oversight in developing countries 

Provision of funds at global, regional and national levels 

CDC contributes market preparation expertise in: 

Assisting countries with surveillance and laboratory capacity to determine disease burden 

Building immunization programs in developing countries 

Advance Market Commitment (AMC) is an example of market preparation incentives. AMC is an 

innovative funding mechanism that provides incentives for private industry to develop vaccines for 

diseases that primarily affect the developing world. With an AMC, donors commit funding to guarantee 

the price of a vaccine once it has been developed, thereby creating a predictable market for the vaccine. 

Developers then make binding commitments to provide vaccines at fixed, lower prices. This benefits 

long-term planning, as developing countries are then better able to develop sustainable financing plans. 

Currently, there is a pilot AMC for the next generation pneumococcal conjugate vaccine that is 

administered through GAVI and the World Bank. Many of the same donors that contribute to GAVI also 

donate to this innovative US$1.5 billion AMC. The USG chose not to participate in this pilot AMC due to 

a variety of concerns around its construct. It is important to note that the AMC financial contribution is 

only a portion of the total funding necessary to get this vaccine into many of the poorest countries. In 

addition to the US$1.5 billion AMC fund, the GAVI board has had to commit a matching US$1.5 billion 

dollars through 2015 to help meet the anticipated demand of the pneumococcal vaccine by GAVI eligible 

countries. It is estimated that GAVI will have to commit several billion dollars after 2015 to continue the 

pneumococcal introduction into additional GAVI eligible countries. As an important donor to GAVI, the 

USG has strong interest in the AMC and its progress. In addition to the multibillion dollar requirement for 

39 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

vaccine purchases, there are substantial, additional financing requirements for technical assistance to 

strengthen routine immunization programs expected to deliver the new, high priced vaccines; to train 

health care workers; for disease surveillance; for cold chain management; and for waste management, 

among other costs. 

Billions of dollars of long-term funding will be required to sustain the introduction of the pneumococcal 

vaccine; however, it will save a large percent of the approximately 1.8 million children under five years 

of age who currently die from pneumonia each year. It appears that the AMC pilot may have helped 

increase the supply of pneumococcal vaccine for developing countries. However, the AMC is only part of 

the answer as the science was firmly in place, with one vaccine already on the market before the AMC 

came to pilot. 

The AMC launch provides a timely opportunity for the USG to learn from an initiative that seeks to 

address the challenges of vaccine availability. The USG will continue to monitor the progress of the pilot 

AMC and other economic incentives, and will engage in the international dialogue on the various 

incentives, as appropriate. A report outlining advance market commitments has been prepared by the 

Department of Treasury in response to the Lantos- Hyde legislation. 

Another market preparation incentive is the priority review voucher (PRV), which is a U.S. specific 

market preparation tool. A PRV can be granted to any company that gains FDA approval for a new drug 

or biological product that addresses a neglected tropical disease. The company that holds this PRV is then 

entitled to receive an expedited FDA review of a future product, which can be transferred – or sold for 

profit – to another company. This expedited review means that a future product would be ready for 

licensure several months earlier, which could translate into tens of millions of dollars in additional 

revenue for the product. 

40 
 

V. Expansion of Public-Private Partnerships and Leveraging 

Resources from Other Countries and the Private Sector 

While the public sector has the expertise and mandate to address the health needs of the underserved, the 

private sector also brings expertise that is essential to meet that mandate. Key vaccine development 

experience and know-how that exists within the private sector include the knowledge on how to conduct 

late-stage product development, the ability to manufacture vaccines to international standards once they 

are developed, and the capability to navigate regulatory pathways. The public sector possesses critical 

expertise in designing and delivering products intended for low-resource settings. For this reason, PDPs 

play an important role by leveraging private-sector expertise and resources alongside public-sector 

experience in addressing the health needs of developing countries. PDPs are designed to fill the product 

development gaps in areas where markets are weak and private industry perceives no opportunity to 

receive a return on their investments in the highly capital intensive R&D process. Moreover, PDPs are an 

efficient way for the USG to leverage private-sector expertise with scarce resources. 

The BMGF has been an integral partner in various PDPs. For the past decade BMGF has invested in 

global health to develop tools and approaches that will have high impact, as well as developed critical 

partnerships and financing mechanisms to ensure that these will ultimately be delivered where they are 

needed most. Partners in their efforts have included bilateral, large and small companies, academia, and 

PDPs. The foundation currently supports 16 PDPs in infectious diseases (see Figure 8 below). 

Figure 8 

1 

Growth of Product Development Partnerships 

PDP era: 

16 PDPs founded in 1999-2003 

Human hookworm 

vaccine initiative 

PDPs begin as an 

experiment 

Last PDP founded: 

2007 

Vaccine Development Program Sources: Combating Diseases Associated with Poverty, FSG, Nov 2004, Health 

partnership Review, Global Forum for Health Research, May 2008 

1993 1995 1997 1999 2001 2003 2005 2007 2009

41 
 

 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

BMGF research and development programs are being funded from discovery through late-stage 

development and into introduction. The level of funding depends on the nature of the disease (global 

versus regional) and demand. The priority list includes: 

The “big 3” – HIV, malaria, and TB – Each have a number of candidate products in a managed 

portfolio that is advancing competitively through the development sequence. The world’s most 

advanced malaria vaccine, termed RTS S, has just entered into Phase III trial in Africa, while the 

first novel TB vaccine entered into Phase II trial this year. The HIV/AIDS field has refocused on 

driving early candidates into proof-of-concept. Given the global priority of these diseases, 

funding of projects and/or PDPs occurs in partnership with other donors (including bilaterals). 

Each field is aligned around a broad global plan (such as the HIV Vaccine Enterprise, the TB 

Partnership, and the Roll Back Malaria program). 

Vaccines to prevent pneumonia – New vaccines to prevent pneumococcus (particularly 

common protein vaccine), influenza, and respiratory syncytial virus, would join the global 

vaccine armamentarium that currently includes measles and Hib. These are urgently needed to 

prevent the number one cause of death in children under five years of age. Prospective 

epidemiologic studies in high burden developing countries are ongoing and may identify other 

priorities for investment. A global market means that there may be opportunities for focusing 

commitments to trials in developing countries that are required for licensure and introduction. 

The new AMC provides a unique opportunity to leverage this market combination to incentivize 

industry to engage in creation of technical solutions for pneumonia. 

Vaccines to prevent diarrhea and other enteric infections – rotavirus, cholera, ETEC, and 

Shigella – Specifically, rotavirus vaccines are now licensed in multiple countries, and GAVI is 

poised to prioritize the introduction of rotavirus vaccine to prevent the most frequent cause of 

dehydrating diarrhea of infancy. 

Vaccines for select neglected tropical diseases – hookworm, trypanosomiasis, and 

cysticercosis – These diseases have traditionally received little attention in terms of R&D 

investments and depend primarily on public and philanthropic sectors – so called push funding – 

for advancement. 

BMGF’s program includes grants to support discovery, development, and delivery of new vaccines. 

Cross-sector partnerships are a key theme of the BMGF program. Partnerships engage the knowledge 

base in each sector and the resources each brings to the table, and allows these to be combined for impact. 

Another example of effective partnerships is specific to HIV through NIAID. NIAID fosters and supports 

public-private partnerships through several grant or contract mechanisms – the HIV Vaccine Research 

and Design program, Integrated Preclinical/Clinical AIDS Vaccine Development program, and HIV 

Vaccine Design and Development Teams. Each of these mechanisms support consortia of researchers 

from the public and private sectors, but the HIV Vaccine Design and Development Teams, in particular, 

funds public-private partnerships of scientists from industry and/or academia to help advance promising 

vaccine concepts. 

42 
 

 

 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Examples of Current Partnerships with Private Industry 

for HIV through NIAID (not inclusive) 

Company Preclinical Research & 

Development 

Support of Clinical 

Trial 

ABL X 

AlphaVax X * 

Althea X ** 

GenVec X ** 

GeoVax X X 

Merck X 

Novartis X * 

Profectus X * 

Sanofi X 

Targeted Genetics X * 

VGX X * 

*Clinical trials in planning phase 

**Products produced under contract in clinical trials 

The NIAID intramural VRC also interacts with industry groups to leverage NIAID research capacity and 

to foster product development initiatives. 

NIAID contributes to the Global HIV Vaccine Enterprise (Enterprise), a “virtual” consortium of 

independent organizations. The Enterprise is committed to accelerating the development of a safe and 

effective preventive vaccine for HIV/AIDS through the creation and implementation of a shared strategic 

scientific plan, mobilization of resources, and greater coordination and collaboration among HIV vaccine 

researchers worldwide. 

The Enterprise seeks to: 

Stimulate the development of increased HIV vaccine manufacturing capacity. 

Establish standardized preclinical and clinical laboratory assessments for candidate HIV vaccines. 

Close the gap between global capacity and future requirements for conducting clinical trials of 

HIV vaccines.
 

Promote greater engagement by scientists from developing countries in the HIV vaccine research 

effort. 

NIAID supported the first Enterprise Scientific Strategic Plan through the creation of CHAVI. NIAID 

also tailors its existing programs to support the priorities identified by the Strategic Plan. As one of the 

leading stakeholders of the Enterprise, NIAID provides financial support to the Enterprise Secretariat. At 

present, the Enterprise is developing a 2010 Scientific Strategic Plan, which will include key scientific 

questions for consideration, a delineation of structural, organizational and capacity-building approaches, 

recommendations for funding, and milestones to measure success. This plan will be guided by an 

advisory board and five working groups, each of which will include representatives from the 

biopharmaceutical industry and leading scientists and advocates inside and outside the field of HIV 

vaccine research and development. 

To ensure global implementation of this plan, NIAID and the Enterprise Secretariat actively foster 

initiatives that will further HIV vaccine research and development in various geographical regions. These 

efforts include the African AIDS Vaccine Program (AAVP), whose mission is to promote HIV vaccine 

development for Africa, through research, advocacy, partnership, and contribution to capacity 

strengthening and policy development, and the AIDS Vaccine Asian Network (AVAN), which strives to 

help develop and strengthen a regional platform for clinical trials, including harmonized legal, regulatory, 

and ethical frameworks. 

43 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

NIAID also supports the efforts of the South African AIDS Vaccine Initiative (SAAVI), which was 

formed in 1999 to coordinate the research, development and testing of HIV vaccines in South Africa. 

SAAVI is based at the Medical Research Council (MRC) of South Africa and is working with key 

national and international partners to rapidly produce an affordable, effective and locally relevant HIV 

vaccine. In 2007, SAAVI collaborated with the NIAID and the HIV Vaccine Trials Network for the 

conduct of a large Phase II vaccine trial in South Africa. Currently, NIAID is supporting the clinical 

assessment of a vaccine developed by SAAVI, the manufacture of which was supported by NIAID. 

NIAID works collaboratively with SAAVI in the support of clinical research sites in South Africa. 

The Partnership for AIDS Vaccine Evaluation (PAVE) was formed in 2003 with the recognition that no 

single entity or institution is likely to succeed alone in the goal to develop a sage and effective HIV 

vaccine. This consortium of USG agencies and USG-funded organizations has a goal of achieving better 

harmony and increased operational and cost efficiencies in HIV vaccine development and the conduct of 

HIV vaccine clinical trials, especially Phase III trials. To accomplish this, PAVE serves as a forum and 

clearinghouse for information sharing and planning. PAVE also aims to eliminate unnecessary 

duplication of efforts, and pools intellectual resources and experience to achieve the fundamental goals 

that a number of USG agencies and others share in common. PAVE has coordinated U.S. Government 

laboratory efforts with a focus on standardization and validation of assays in support of clinical trials 

internationally, spearheaded efforts to determine critical clinical site needs and to catalogue clinical trial 

sites both domestically and in the developing world, contributed to novel trial designs, facilitated 

communication, and harmonized critical path clinical trials. Of note, this partnership led to the successful 

harmonization of active international trials across several of the partners. Although not implemented, the 

planning and preparation of PAVE 100, a large Phase IIB trial, marked a major success in scientific and 

operational coordination and collaboration among all the member organizations, which should be of great 

significance for future efforts. Additional information can be found at www.hivpave.org. 

NIAID is also able to leverage resources in other countries by working closely with the MHRP for the 

conduct of HIV vaccine trials. The U.S. Military HIV Research Program (MHRP) provides access to a 

large number of sites overseas and a comprehensive medical infrastructure, particularly in Africa and 

Thailand. 

Given the robust evidence that exists on the impact of safe and efficacious vaccines, forcing a choice 

between investments in R&D versus introduction of existing vaccines is a false dichotomy. The current 

economic environment does create challenges, but the first principles for global health should not be 

forgotten: the concept of equity, the value of prevention, and the known scalability and potential of 

success of vaccine programs. The case for investment in both R&D and implementation of vaccines has 

been amply documented as excellent global health “buy.” 

The business model for engagement varies by disease and its unique epidemiology. Vaccines for global 

diseases – such as pneumonia – have a global market, and thus it is possible to enter into agreements that 

would leverage that market to ensure global access; in this context, industry makes its own investments 

but it is often critical to provide resources to ensure collection of data to support safety and efficacy under 

conditions of poverty and other tropical diseases. In contrast, vaccines for orphan diseases, which may be 

geographically limited (trypanosomiasis; or even a developing country clade of HIV) and often affect 

those in poverty, are usually doomed to market failure. Development of these vaccines depends largely on 

government and philanthropic funding for success. It is challenging for large companies to invest in R&D 

for neglected diseases, but there are well developed public-private partnerships for malaria and neglected 

diseases that have overcome these constraints. While developing-country manufacturers can often create a 

viable business model for themselves with large volume and low prices, they have less experience with 

generating innovation and de novo development, although this is changing. 

One of the most pressing problems that this global vaccine enterprise is facing is the challenge of having 

multiple candidates prepared for advanced trials in endemic countries. This poses two problems: first, the 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

problem of field trial capacity and second, the financial requirements of such a program. If the NIH is 

successful in extending engagement of the field trial capacity it has created in HIV endemic areas for 

evaluation of other global health products, this may ease the capacity constraints. Managing the financial 

requirements to drive the portfolio of priority global health products will require rigorous prioritization, 

cross-disease collaborations, as well as additional funds. While the PDPs are prepared to collaborate, 

aligning the donors, partner countries and academic organizations behind the most effective use of this 

critical capacity will be a priority for the coming years. 

There are investments needed in enabling infrastructure, particularly regulatory systems that need to be 

prepared to evaluate and approve the new global health products. This has become a priority for the 

countries themselves. Success would mean fewer delays and thus a cost-savings for the entire system. 

The USG commitment to accelerating the development of vaccines for global health is critical for success 

of this effort. Drawing upon the innovation generated by support from NIH, engaging the specialized 

experience and knowledge of MHRP, partnering with USAID in the support of PDPs to discover and 

evaluate candidates in the field – there are a multitude of examples to indicate that USG engagement has a 

long and without question the most productive history of contributions to vaccine discovery of any 

country. A few examples: development of conjugate technology by NIH; generation of candidate malaria 

vaccines by the U.S. Military HIV Research Program (MHRP); and creation of new partnerships for 

evaluation of rotavirus vaccines by USAID. These are but a few examples that demonstrate the power of 

the U.S. public and private vaccine development framework. It is upon these successes that overcoming 

the remaining, even tougher challenges – such as an HIV or an effective malaria or TB vaccine – depend. 

PDPs can address various hurdles in the vaccine development pipeline. They have played a key role in 

vaccine development and will continue to do so in the future. The long-term nature of product 

development requires long-term, sustainable, and predictable funding to ensure that the most effective 

vaccine candidates can progress in a timely manner through the full spectrum of clinical development. 

The variety and number of current PDPs makes it necessary to study whether additional PDPs are 

required to accelerate the development of vaccines or whether the need lies in expanding already existing 

PDPs. As such, as part of the USG strategy to accelerate the research, development and manufacturing of 

vaccine, the USG will explore the range of vaccine development partnerships to determine the most 

efficient way for the USG to leverage private-sector expertise with scarce resources. 

GAVI Alliance 

The GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization) was launched in 2000 

to improve access to immunization for children in impoverished countries. GAVI does not invest in 

vaccine R&D, but focuses on introducing vaccines into country programs and providing funding for 

strengthening health systems. As a result, nearly 3.4 million deaths may have been averted since 2000. 

Governments in developed and developing countries, UNICEF, WHO, the World Bank, the BMGF, 

nongovernmental organizations, civil society, vaccine manufacturers from developed and developing 

countries, and public health and research institutions work together as partners in the alliance to support 

the poorest 72 countries of the world (GNI per capita of less than US$1,000 as of 2003 World Bank data). 

Since 2001, USAID has provided US$569 million to GAVI; donors such as the Bill & Melinda Gates 

Foundation, developed and developing country vaccine manufacturers, research and technical institutes, 

bilateral and multilateral institutions, and civil society organizations have committed roughly US$2.5 

billion through 2015. 

GAVI supports the introduction of under-utilized vaccines to the poorest countries of the world. Its 

greatest success to date has been the widespread introduction of Hepatitis B (Hep B) and Haemophilus 

influenzae type b (Hib) vaccines. These vaccines have been widely available in developed countries for 

decades but beyond the financial reach of the poorest countries. Since inception, GAVI financing has 

provided: 

45 
 

Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Hep B vaccine to 192 million children 

Hib vaccine to 42 million children 

DTP vaccine to 51 million children 

For the past seven years, GAVI focused its resources to reduce the introduction time for two vaccines: 

pneumococcal conjugate vaccine and rotavirus vaccine. The successful introduction of these vaccines 

could substantially reduce the 800,000 deaths of children under-five attributed annually to pneumonia and 

the approximately 250,000 annual deaths of children under-five caused by rotavirus. These two projects 

focused on elevating the profile of the disease mortality, discovering what country-level decision-makers 

knew about the diseases, generating missing data on disease burden in developing countries, and 

analyzing and addressing vaccine supply related issues. Two developing countries have introduced an 

early version of pneumococcal conjugate vaccine (PCV7); and an additional 11 countries have been 

approved by GAVI to receive the newer version with additional serotypes in 2010–2011. GAVI has also 

supported the introduction of rotavirus vaccine in four countries; nine additional countries have been 

approved for introduction starting in 2010. 

GAVI is also having an impact on the vaccine industry by demonstrating to vaccine manufacturers that a 

profitable developing-country market exists. Armed with substantial, predictable resources and the ability 

to negotiate longer-term supply commitments with industry, GAVI has generated reliable demand in 

developing countries for existing vaccines (Hep B, Hib and yellow fever in particular) and is working on 

improving rapid access for new vaccines. New, complex vaccines are costly, and GAVI will need to 

attract greater funding to provide for their sustained introduction so that industry will invest in vaccines 

for developing countries. 

Funding will also be needed to build immunization programs and health systems to deliver the new 

complex, expensive vaccines. GAVI has demonstrated that a combination of funds for the purchase of 

vaccines for developing countries combined with credible country-level demand forecasting and multipartner coordination can induce industry to provide a greater supply of newer vaccines at lower prices. 

Vaccine purchases alone do not get vaccines into children or their intended population. USAID and CDC 

continue to invest in routine immunization programs in developing countries to build the capacity of 

national and local governments and partners to deliver vaccines. Countries need to be prepared at the 

national and the local level for the introduction of new, expensive vaccines. Without robust immunization 

programs, investments in vaccine research and development and procurement will fail. 

46 
VI. Efforts to Maximize United States Capabilities 

to Support Clinical Trials of Vaccines 

in Developing Countries and to Address the Challenges 

of Delivering Vaccines in the Developing Countries 

Clinical Trials of Vaccines in Developing Countries 

The U.S. Government plays a significant role in supporting vaccine clinical trials and effective delivery of 

vaccines in the developing world. NIH is a leading agency in supporting clinical trial sites worldwide. An 

example of their leading efforts can be found in NIH’s R&D HIV vaccine portfolio. Specifically, NIH 

continues to conduct and/or support clinical trials of vaccine candidates through the HIV Vaccine Trial 

Network (HVTN) and the NIAID Dale and Betty Bumpers Vaccine Research Center (VRC), as well as 

through collaborations with the Military HIV Research Program (MHRP). The Fogarty International 

Center supports extensive training opportunities for international investigators in many prospective 

vaccine trial sites. NIAID’s active involvement with the Partnership for AIDS Vaccine Evaluation 

(PAVE) and the South African AIDS Vaccine Initiative (SAAVI) also increase its ability to conduct HIV 

vaccine trials in developing countries and address issues and needs specific to a given region. The 

participation of international sites (see Figure 9 below) and the involvement of diverse populations 

through partnership with host country researchers, governments, and communities are critical components 

of NIAID’s HIV vaccine effort. They allow for studies that examine differences in HIV diversity, genetic 

background, nutritional status, effects of other infections, and access to health care, all of which may 

prove crucial to developing an effective vaccine for use around the world. 

NIAID and the HVTN have actively helped to develop sustainable sites in the developing world and 

continue to support those efforts, exploring avenues to make the activity and support of those sites more 

robust. The HVTN works closely with community members and programs to educate people about 

HIV/AIDS, HIV vaccine research, and the importance of clinical trials. Through close collaboration with 

communities where vaccines will be tested, the HVTN hopes to enroll a diversified population in its 

clinical trials, ensuring access and representation of populations most affected by HIV. Additional 

information can be found at www.hvtn.org. 

The DoD is also a key USG agency supporting clinical trial sites. Established in 1985 to protect troops 

entering endemic HIV areas, the MHRP is part of the Walter Reed Army Institute of Research, U.S. 

Army Medical Research and Materiel Command. It brings together scientists from the U.S. Army, Navy, 

and Air Force and is closely partnered with the Henry M. Jackson Foundation for the Advancement of 

Military Medicine. NIAID jointly plans and executes HIV/AIDS research projects and clinical trials with 

the MHRP through an interagency agreement. This collaboration helps ensure that USG HIV vaccine 

research is well coordinated, efficient and comprehensive, and allows NIAID access to DoD’s presence 

overseas, particularly in Africa and Thailand, including the extraordinary DoD medical infrastructure and 

extensive knowledge in establishing and supporting operations in underdeveloped areas. Through this 

partnership with NIAID, the MHRP, the primary HIV/AIDS research program for DoD, jointly plans 

HIV/AIDS research that includes the design and construction of vaccine candidates, preclinical research 

and development, pilot lot production, and Phase I-III human clinical testing of safety, immunogenicity 

and efficacy of HIV candidate vaccines and vaccine strategies. Additional research is also conducted as 

required to develop the necessary local capacity to support these vaccine clinical trials and identify 

effective preventive measures. In September 2009, the first HIV vaccine efficacy trial supported by 

NIAID, conducted in Thailand in collaboration with the MHRP, reported that the investigational HIV 

vaccine regimen was safe and modestly effective in preventing HIV infection, proving a concept that is 

sure to lead to improved vaccine candidates. Additional information can be found at 

www.hivresearch.org. 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

Another HIV vaccine efficacy trial started in June 2009 will evaluate the product concept developed at the 

intramural NIAID VRC. The study (HVTN 505) will be conducted by the NIAID-funded HVTN sites and 

is expected to have the first endpoint analysis in 2012. 

Figure 9 

As part of its collaboration with USAID, IAVI is committed to building sustainable capacity in the 

developing world and is collaborating with scientists in Kenya, Uganda, and South Africa to test vaccine 

candidates in clinical trials. USAID is working with IAVI to explore how capacity building by IAVI for 

preparation of clinical trial sites in developing countries can be leveraged to support the roll-out of 

HIV/AIDS treatment, care, and prevention, especially under PEPFAR. Conversely, new HIV/AIDS 

treatment programs can be beneficial for large-scale vaccine trials. During the enrollment period of Phase 

III (efficacy) vaccine trials, it is likely that large numbers of people will be screened who are in 

immediate need of antiretroviral therapy. Having convenient treatment available and appropriate referral 

mechanisms in place will help the trials ensure positive relations with the communities where they are 

conducted. 

In addition, USAID collaborates with the NIH, CDC, and MHRP through PAVE, as described above. In 

2008, IAVI, with the CDC and MHRP, released landmark work to provide data defining normative 

laboratory values. Across Africa, drug and vaccine trial participants, for diseases such as HIV/AIDS, TB 

and malaria have been routinely disqualified from studies due to the standard use of laboratory reference 

ranges developed for Western populations. Laboratory tests on kidney and liver functions as well as blood 

counts (e.g., hemoglobin, neutrophils and eosinophils) of healthy African men and women, often fall 

outside established ranges. Researchers believe that these differences are largely environmental in nature 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

– people in Africa encounter common parasites and pathogens not typically found in the Western world. 

The immune cells (CD4) responsible for fighting off infections, which HIV targets and are an important 

measure of AIDS progression, thus tend to be somewhat lower. 

It is of critical importance that clinical trials are conducted among the intended recipients to assure that 

the vaccine or drug works. Due to the work of IAVI and its partners, reference ranges for healthy African 

trial volunteers have been established, creating appropriate criteria for the inclusion and exclusion of 

volunteers in testing for new, preventive health technologies, accurate health monitoring of patients 

throughout the course of a clinical trial, and, importantly, to guide treatment. This new data is critical in 

the design and monitoring of clinical trials, particularly trials of potentially life-saving technologies, 

among African populations. 

IAVI’s work also builds local capacity at trial sites in human resources, laboratory, clinical, IT, and other 

sustainable infrastructure. Their work results in reliable incidence and prevalence estimates through 

extensive cohort studies that define early HIV infection immunologic events and guide decisions on 

where large-scale efficacy trials may be possible for vaccines and other new prevention technologies. 

USAID advisors ensure that IAVI establishes referral patterns to interface with existing USG programs 

for HIV/AIDS treatment, care, and prevention services under PEPFAR and the Global Fund to Fight 

AIDS, Tuberculosis and Malaria while strengthening the capacity to accelerate clinical trials of HIV 

vaccines in developing countries. These synergies set the stage for eventual product introduction and 

distribution. To adequately inform public policy, USAID’s partnership with IAVI supports analytical 

models to forecast global demand estimates for HIV vaccines. 

The information above provides examples of USG support specific to HIV; however the USG is also 

involved in clinical trial sites in other diseases including malaria and TB. The USG is committed to 

building sustainable capacity in the developing world and is already collaborating with scientists in 

countries such as Kenya, Uganda, and South Africa to test vaccine candidates in clinical trials. To 

accelerate the development of vaccines for infectious diseases, the USG will strengthen coordination 

among the various programs that are supporting clinical trials for infectious diseases. Coordination among 

programs conducting research in the same disease area is already quite strong and will continue to provide 

a strong base for continued clinical trials. There is opportunity to have more synergies across different 

disease areas. For example, there may be HIV clinical trial sites that can benefit from collaboration with 

TB clinical trial sites in the same country or region. This cross fertilization may be already occurring; 

however, it is necessary to ensure that all opportunities have been maximized. As such, to accelerate the 

development of vaccines, the U.S. Government will conduct a mapping exercise of all vaccine clinical 

sites that are implemented by or funded by the USG. More robust information of the relevant clinical trial 

sites will lead to more strategically coordinated, streamlined and aligned government support for 

advancing the development of new vaccines for infectious diseases. 

Addressing Challenges of Delivering Vaccines 

in Developing Countries 

The delivery of vaccines in developing countries is far more complex than many people imagine. Buying 

vaccine is only one piece of a complex puzzle. Vaccine delivery preparedness actually often times begins 

years before the vaccine is actually introduced into a country program. Disease burden needs to be 

established through surveillance and laboratory capacity. Awareness must be raised if it is a disease that is 

difficult to understand or detect. Arguments must be made around cost effectiveness. Ministries of Health 

have to work with Ministries of Planning and Finance to figure out how and when they can afford to bring 

a vaccine into the program. Regulatory authorities need to be in a position to determine if a vaccine is 

appropriate for their population, that it is safe and effective. The regulatory authority must be sufficiently 

strong to know how and when to address an adverse event after immunization. Logisticians must 

determine if there is sufficient cold chain capacity for storage at national, regional and local levels and 

49 
Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

determine how and how often they will have to transport the vaccines safely in a cold chain. Health 

workers must be trained on a number of issues such as how to administer the vaccine, counsel parents on 

timing of doses and what to look for if there were a reaction to the immunization. Communities must be 

informed of new vaccines. Doses must be calculated with wastage rates, orders placed and paid for, all 

before a dose is ever administered. The above steps are required in order to deliver vaccine, and all take 

place with the assumption that the immunization program is sufficiently strong to reach the targeted 

population through careful planning of fixed site immunization or planned periodic intensification. 

Delivering a vaccine to the target population is only one step of many required in an immunization 

program. There is a great deal of work that remains to be done across all these areas for immunization 

programs in developing countries to overcome the challenges of safely delivering vaccines to their target 

populations. 

The quality of immunization programs in developing countries is variable. Some very poor countries have 

dedicated themselves to building systems that are able to reach a very high percentage, even 95%, of their 

birth cohort with three or four visits in the first months of life. Other countries are barely able to reach 

25% of their children with three visits in the very early months of life. Few countries have immunization 

programs that extend to reaching children through school-based immunization at strategic ages. 

Both USAID and CDC work to build capacity in developing countries to continue to improve 

immunization programs because without them vaccines simply cannot be delivered. USAID’s primary 

investment in immunization is through GAVI where the focus is largely on the purchase of new and 

under-utilized vaccines with some additional investments in strengthening health systems. In addition, 

USAID makes technical assistance available to USAID regional offices and country level USAID 

missions worldwide to strengthen immunization programs. USAID works closely with national, district 

and local governments, WHO, UNICEF and civil society in-country to help build programs. USAID also 

provides short term specific assistance with a component of the immunization program like supportive 

supervision, planning, training, logistics or assessments and evaluations to prepare for applications to 

GAVI. USAID also supports programs that strengthen routine immunization systems and provide 

technical assistance to countries to introduce new and underutilized vaccines. 

The expertise of USAID staff is oftentimes tapped at the global and regional level to help inform 

decision-making at important decision points. USAID makes strategic investments in supporting quality 

supply globally, providing high-level immunization advisors to strategic countries through WHO, 

twinning strong regulatory agencies with weak ones in developing countries, and funding specific 

economic studies on the cost effectiveness of a vaccine compared to the economic devastation of disease. 

Some USAID missions support immunization programs through provision of immunization advisory staff 

or disease surveillance or laboratory support while others contribute short-term assistance, financial or 

technical, in the case of epidemics, outbreaks or campaigns. 

CDC supports immunization programs in developing countries by providing their technical expertise to 

assist with evidence-based decision-making regarding the introduction of new vaccines and to support 

program implementation and monitoring of the impact of vaccines. CDC deploys its epidemiologists, 

public health experts, and scientists to WHO, UNICEF, and other international organizations, where they 

hold leadership positions in global, regional, and country-level immunization programs and help ensure 

the effective delivery of vaccines to achieve optimal coverage. In addition, CDC helps countries to 

introduce new and underutilized vaccines into routine immunization systems by assisting with studies that 

measure disease burden, providing epidemiologic and laboratory expertise to strengthen country capacity, 

as well as new vaccine safety, effectiveness, and cost-effectiveness analyses; conducting postintroduction studies to show when reductions in disease incidence have occurred and the value of the 

vaccine relative to the cost of sustaining the vaccine program; and supporting national vaccine advisory 

committees to enhance data-driven decision-making, including evaluating scientific, programmatic and 

economic aspects of vaccine introduction. 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

CDC is also engaged in strengthening routine immunization systems in resource-poor countries. Key 

activities include providing technical and financial assistance to partners at the global, regional, and 

national levels as well as directly to Ministries of Public Health to define and implement the most 

effective immunization strategies (such as the Reaching Every District strategy) for a country’s individual 

circumstances; improving the planning of immunization services; strengthening national capacity 

building, monitoring, and data collection systems to develop effective program policies. These efforts at 

strengthening routine immunization systems are supplemented through providing technical assistance to 

partners and countries to help implement new global, regional and national goals to eradicate, eliminate, 

or control polio, measles, rubella, hepatitis B, and neonatal tetanus. 

Industry has made it clear that delivery of existing vaccines through robust immunization programs is 

important to them as a consideration for developing additional vaccines for use in developing countries. 

Developing countries with little commitment to immunization as a priority health intervention, inadequate 

vaccine policies, weak health systems, weak financial systems, poor disease surveillance systems, 

inadequate cold chain, and a lack of personnel to deliver vaccines are hurdles industry cannot address. 

Industry wants the USG and the global vaccine community to continue their work with developing 

countries to build capacity and improve public health programs. 

Through USAID and CDC, the USG is currently providing technical assistance to developing countries to 

ensure access and availability of lifesaving vaccines once vaccines are available. As described above, 

USAID’s primary investment in immunization is through GAVI, where the focus is largely on the 

purchase of new and under-utilized vaccines with some additional investments in strengthening health 

systems. GAVI has been successful in increasing the availability of new and underused vaccine to 

developing countries. However, this investment alone will not get the vaccines into children. To ensure 

country preparedness for vaccines, USAID and CDC have continued to invest in supporting routine 

immunization programs in developing countries; helping to build capacity of national and local 

governments and partners to deliver vaccines through their programs. More work is needed to continue to 

build the capacity of developing countries, especially with new and expensive vaccines being made 

available to developing countries. As such, the U.S. Government will continue its efforts to support 

routine immunization systems and build the capacity of developing country governments. 

51 

VII. Coordinated Strategy 

The U.S. Government is engaged in coordinated strategies with partners the world over to accelerate 

development of vaccines for infectious diseases, such as HIV/AIDS, malaria, and tuberculosis, and to 

deliver vaccines to people in developing countries. Each USG agency’s mandate, funding level, and 

availability of expertise determines where they are engaged on the continuum from basic research through 

delivery and immunization in developing countries. 

In response to the three specific areas of review that were requested to be included in this report, the study 

group recognized: 

i.	 Initiatives to create economic incentives for the research, development, and manufacturing 

of vaccines for HIV/AIDS, tuberculosis, malaria, and other infectious diseases. There are a 

range of incentives and innovative financing mechanisms in early phases of implementation and 

others that are being explored. These mechanisms have the potential to stimulate accelerated 

research and development of vaccines. However, before increased commitment by the USG, the 

various mechanisms require further study to determine which mechanisms are most appropriate 

and feasible for investment. The USG will continue to consider options specific to U.S.-based 

R&D and manufacturing, while monitoring the progress of the pilot Advanced Market 

Commitment and other economic incentives. 

ii.	 An expansion of public-private partnerships and the leveraging of resources from other 

countries and the private sector. USG agencies are engaged with a variety of partners from 

academia, industry, UN agencies, civil society, developing countries, and product development 

partnerships (PDPs). An expansion of public-private partnerships and the leveraging of resources 

from other countries and the private sector could accelerate the development of vaccines. The 

variety and number of current PDPs make it necessary to determine whether additional PDPs are 

required to accelerate the development of vaccines or whether the need lies in expanding existing 

PDPs. As such, as part of the USG strategy to accelerate the research, development and 

manufacturing of vaccines, the U.S. Government will explore the range of vaccine development 

partnerships to determine the most efficient way for the USG to leverage private-sector expertise 

with scarce resources and strategically engage in supporting the indirect determinants around 

market preparation. 

iii.	 Efforts to maximize U.S. capabilities to support clinical trials of vaccines in developing 

countries and to address the challenges of delivering vaccines in developing countries to 

minimize delays in access once vaccines are available. USG agencies engaged in vaccine R&D 

and immunization delivery are well coordinated and work strategically within individual vaccine 

areas. However, across vaccine areas more information-sharing and joint strategic development 

need to take place. The USG has actively developed sustainable clinical trial sites in the 

developing world over many years and works to continue to make those sites more robust, as 

more complex clinical trials for vaccines against more complex diseases are required. To 

accelerate the development of vaccines, the USG will build upon what was accomplished by the 

Partnership for AIDS Vaccine Evaluation (PAVE) for HIV vaccine trial sites and will conduct a 

mapping exercise of all vaccine clinical sites that are implemented by or funded by the U.S. 

Government. More robust information on the relevant clinical trial sites will lead to more 

strategically coordinated, streamlined, and aligned government support for advancing the 

development of new vaccines for infectious diseases. Delivering vaccines in developing countries 

is complex. Public health impact is not achieved when the vaccine is developed but rather when it 

reaches the intended population in developing countries. The U.S. Government will continue to 

program in a strategic and complementary fashion to build immunization program capacity in 

developing countries. 

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Coordinated Strategy to Accelerate Development of Vaccines for Infectious Diseases 

In order to coordinate the acceleration of the development of vaccines for infectious diseases, USG 

agencies will continue to convene a study group or groups around the strategy to further engage across 

disease specific areas. Each USG agency engaged in global health research plays a distinct role at 

different stages of research, and nongovernmental partners provide unique expertise in vaccine 

development. For this reason, a study group or groups will meet at regular intervals to continue 

collaboration to accelerate vaccine development, to share information on vaccine development efforts, 

and to maximize the synergies that are created from working in a more coordinated manner. The rate of 

progress in each area of vaccine research, development, and delivery will be proportional to resources 

available. 

54 
U.S.Agency for International Development 

1300 Pennsylvania Avenue, NW 

Washington, DC 20523 

www.usaid.gov