Recent Developments in NIAID Pandemic Influenza Research 

The NIAID Pandemic Influenza Preparedness Program supports research in basic biology, 

surveillance and epidemiology, vaccine development and evaluation, and the development of 

antivirals against influenza. 

Below is an overview of NIAID-supported research and global events dating back to 1997, when 

the word’s first known cases of human infection with avian influenza viruses were documented. 

YEAR RESEARCH DEVELOPMENTS & GLOBAL EVENTS 

1997 

- In August, avian influenza (H5N1) infections occur in both poultry and humans 

in Hong Kong. This is the first time an avian influenza virus has ever been found 

to transmit directly from birds to humans. The virus kills six out of 18 people 

infected. All poultry in Hong Kong is culled. (WHO) 

- NIAID awards a grant to Baylor College of Medicine (PI, Pedro Piedra) to 

examine whether vaccinating a large percentage of children can protect a 

community from a possible influenza pandemic. 

1998 

- NIAID awards a contract to Protein Sciences Corporation (PI, John Treanor) for the 

production of a recombinant H5 hemagglutinin vaccine. Within three weeks, the 

company produces an investigational vaccine which is tested in NIAID-supported 

clinical trials. (Related Article) 

- NIAID awards the "Influenza Pandemic Preparedness in Asia" contract to St. Jude 

Children's Research Hospital (PI, Dr. Robert Webster) to: 

• Establish an animal influenza surveillance center in Hong Kong 

• Determine the molecular basis of transmission of avian flu viruses 

• Provide characterized viruses suitable for vaccine development 

• Support training of new laboratory personnel 

• Produce reagents 

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Recent Developments in NIAID Pandemic Influenza Research 

- NIAID-supported scientists discover that human influenza A viruses employ the 

enzyme plasmin to help chop hemagglutinin in two. The discovery may explain what 

amplifies the disease-causing power of influenza A virus and makes the virus 

uncommonly deadly. (Related Article) 

1999 - NIAID awards a grant to the University of Wisconsin (PI, Dr. Yoshihiro 

Kawaoka) to investigate the molecular mechanisms of influenza pandemics. 

NIAID-supported researchers for the first time succeed in engineering an 

influenza A virus entirely from cloned genes, a breakthrough that could 

lead to improved influenza vaccines and new influenza-based gene delivery 

systems. (Related Article) 

- NIAID-supported researchers at St. Jude Children's Research Hospital and 

the University of Wisconsin demonstrate that a new DNA-based vaccine 

protects mice from experimental challenge with the H5N1 virus. (Related 

Article) 

- In March, H9N2 infects two children in Hong Kong. Both children recover. 

(WHO) Meanwhile, in Italy, a two-year H7N1 epidemic begins in the country's 

bird population. The H7N1 virus, originally of low pathogenicity, mutates in less 

than a year to a highly pathogenic form. More than 13 million birds die or are 

culled. (WHO) 

2000 

- NIAID's Vaccine and Treatment Evaluation Units (VTEUs) conduct 

a clinical trial to compare the immune responses of healthy adults who 

receive either a full dose or a half dose of flu vaccine. (Related Article) 

- NIAID awards the following three challenge grants to industry 

partners for vaccine development: 

• NIAID awards a grant to Aviron for the production of a live 

attenuated vaccine for pandemic preparedness and to 

develop a cell culture-based flu vaccine (PI, Dr. Shengqiant Li). 

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Recent Developments in NIAID Pandemic Influenza Research 

• NIAID awards a grant to Aventis Pasteur for the DNA-based 

generation of avian influenza virus vaccines (PI, Fred 

Vogel). The project goal is to use a DNA-based system to 

rapidly produce influenza vaccine candidates, including those 

against H5 and/or H7 pandemic influenza, which will be tested 

in clinical trials by NIAID. 

• NIAID awards a grant to Novavax (PI, Dr. Louis Potash) to 

produce several non-egg-grown influenza vaccines, with the 

goal being that the most promising will be prepared for use in 

clinical trials by NIAID. 

- NIAID-supported researchers at St. Jude Children's Research 

Hospital streamline the use of reverse genetics down to eight plasmids 

- one for each gene in the virus genomes - making the process simpler 

and less expensive. (Related Article) 

- NIAID-supported scientists take part in the Options for the Control 

of Influenza IV Meeting, held in Greece, September 23-28, 2000. The 

meeting objectives are to review the latest advances in molecular 

virology and pathogenesis of influenza viruses and relate them to the 

problems of surveillance, rapid diagnosis and improvement in 

strategies for the treatment and prevention of influenza. 

2001 - St. Jude scientists and University of Hong Kong (HKU) collaborators detect 

the re-emergence of H5N1 in live bird markets in Hong Kong. More than one 

million birds are culled and "market rest day" is instituted. (Related Article). 

Researchers also identify quail as the mixing vessel for the spread of avian 

influenza viruses from aquatic birds to land-based poultry. Live quail is banned 

from live-bird markets the following year. (Related Article) 

- NIAID-funded investigators at the University of Wisconsin use reverse 

genetics to discover that the PB2 gene is key to the virulence of the H5N1 

influenza strain. This discovery provides important information that may be 

useful in understanding the emergence of future viruses that may have 

pandemic potential. (Related Article) 

- In July, NIAID sponsors the Reverse Genetics Workshop (Executive 

Summary), bringing together an international group of researchers in influenza 

viruses as well as scientists outside of the influenza field with research 

experience in other human viruses, biosafety, and public policy. The Workshop 

discussions are centered on using local biosafety committees to examine the 

research work that will be done at federally funded universities and to make 

risk assessments and safety recommendations. 

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Recent Developments in NIAID Pandemic Influenza Research 

2002 - St. Jude scientists and HKU collaborators detect the second re-emergence of 

highly pathogenic H5N1. More than 20 farms are found to be infected and 

more than seven different H5N1 genotypes are identified in wild aquatic birds. 

(Related Article) 

- St. Jude scientists determine that the H5N1 avian virus that killed six people 

in 1997 can bypass natural host defenses, which may explain the high lethality 

of avian strains. (Related Article) 

- NIAID awards a grant to the American Registry of Pathology for the complete 

characterization of the 1918 influenza virus (PI, Dr. Jeffrey Taubenberger). 

(Related Article) 

- Following an outbreak in May of H7N2 among poultry in the Shenandoah 

Valley, Virginia, poultry production area, one person is found to have serologic 

evidence of infection with H7N2. (CDC) 

2003 - St. Jude scientists and HKU collaborators discover that H9N2 viruses 

are endemic in land-based birds in China. (Related Article). It is also 

discovered that gene segments of H9N2 flu viruses found in ducks 

had undergone many changes, with some new combinations coding for 

antigens that could infect humans. (Related Article) 

 

 

- In FY 2003, NIAID expands its Pandemic Preparedness in Asia

contract. This expansion supports enhanced animal influenza 

surveillance sites in Asia, the generation of high-yielding pandemic 

vaccine candidates, and studies of a newly emerging influenza strain 

infecting swine in the United States. (Related Article) 

 

- In September, NIAID convenes an international workshop on the 

Development of a Clinical Trial Plan for Pandemic Influenza 

Vaccines (Meeting Summary) to: 

• Review data from earlier trials of pandemic influenza vaccines 

• Identify manufacturing and regulatory hurdles 

• Prioritize pandemic influenza virus subtypes 

• Develop an agenda for the conduct of clinical trials 

• Initiate development of a U.S. Pandemic Influenza Vaccine 

Protocol 

- NIAID awards a grant to Stanford University (PI, Dr. Ann Arvin) to 

study vaccine-induced and naturally acquired influenza A 

immunity as a model for in-depth analysis of the innate and adaptive 

immune response in children and adults. 

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Recent Developments in NIAID Pandemic Influenza Research 

- NIAID awards a grant to the University of Maryland to understand the 

transmissibility of influenza A viruses (PI, Dr. Daniel Perez). The 

project's objective is to study the interspecies transmission of avian 

influenza viruses. 

 - NIAID awards three grants to industry partners for influenza product 

development: 

• NIAID awards a grant to the Massachusetts Institute of 

Technology to investigate RNA interference of influenza 

virus infection (PI, Jianzhu Chen) as a new way of preventing 

and treating influenza infection. (Related Article) 

• NIAID awards a grant to Dynavax Technologies Corp. (PI, Gary 

Van Nest), to find a relatively stable component for use in a 

new kind of more broadly protective influenza vaccine. The 

vaccine candidate combines an internal flu protein that is less 

likely to be altered through mutation, NP, with a bioengineered 

molecule called an immunostimulatory DNA sequence, or ISS. 

(Related Article) 

• NIAID awards a grant to the University of Colorado at Boulder 

for the development of a diagnostic microarray for 

influenza A (PI, Kathy Rowlen), which may serve as a rapid 

diagnostic. The project's goal is to develop the "Flu Chip," that 

will provide information as to whether or not an individual is 

infected with influenza as well as provide both type and 

antigenic sub-type characterization of the virus. 

- NIAID-supported researchers at the Vaccine and Treatment 

Evaluation Units at the University of Rochester and Baylor College of 

Medicine test an experimental vaccine to protect people against an 

H9N2 bird flu. Clinical trials are completed and results are expected in 

early 2005. 

- NIAID conducts a Phase II study to evaluate the first trivalent 

baculovirus-based recombinant influenza virus vaccine. The 

vaccine, produced by Protein Sciences, was evaluated in healthy 

elderly subjects and was shown to be safe and well tolerated. The 

vaccine may also provide a suitable cell culture system for the largescale production of influenza virus vaccines as a viable alternative to 

the production of the vaccines in eggs. 

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Recent Developments in NIAID Pandemic Influenza Research 

- In February, two cases of avian influenza (H5N1) infection occur in a 

Hong Kong family that had traveled to southern China, resulting in one 

death. Less than two months later, a widespread outbreak of H7N7

occurs on poultry farms in the Netherlands, killing a veterinarian. Cases 

of mild disease or conjunctivitis associated with H7N7 are reported in 

more than 80 other individuals during this outbreak. (WHO) Later the 

same year in New York, a patient is admitted to a hospital in November 

with respiratory symptoms, recovers, and goes home after a few week. 

Subsequent confirmatory tests conducted in March 2004 show that the 

patient had been infected with an H7N2 avian influenza virus. (CDC). In 

December, Korea reports an outbreak of avian influenza in chickens, 

verified to be H5N1, and more than one million chickens are infected. 

(WHO). That same month, a child in Hong Kong is infected with H9N2

and recovers. (WHO) 

2004 

- NIAID supports animal influenza training courses in Hong Kong and 

Japan. 

 

- In 2004, NIAID awards challenge grants to six industry partners to 

develop new diagnostics, therapeutics, and vaccines against influenza 

virus: 

- 1) Shire Biologics, Inc., for the development of a tissue 

culture-derived influenza vaccine (PI, Jonathan Seals). 

- 2) Delsite Biotechnologies, Inc., for the development of an 

inactivated intranasal influenza vaccine (PI, Yawei Ni). 

- 3) Biota Scientific Management, for the development of a 

novel long-acting influenza antiviral drug (neuraminidase 

inhibitor) (PI, Jane Ryan). 

- 4) Columbia University/Griffin Analytical Technologies for the 

development of new diagnostics (PI, Walter Lipkin) to 

discriminate between several pathogens including influenza 

and SARS. 

- 5) University of Texas at Austin/Radix BioSolutions for the 

development of new diagnostics (PI, Steven Kornguth) to 

discriminate between several pathogens including influenza 

and SARS. 

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Recent Developments in NIAID Pandemic Influenza Research 

- 6) BD Diagnostics (PI, Tobin Hellyer), for the development of 

new diagnostics to discriminate between several pathogens 

including influenza and SARS. 

- NIAID awards contracts to Aventis Pasteur and Chiron 

Corporation to support the production of an investigational vaccine 

based on a strain of H5N1 avian influenza. The vaccines will be tested 

for safety and immunogenicity in Phase I and Phase II clinical trials 

conducted by NIAID's Vaccine and Treatment Evaluation Units 

(VTEUs). Studies will test the vaccine in healthy adults first with 

subsequent studies planned in children and the elderly. 

- NIAID awards a grant to Washington University for the M2 Peptide 

Based Vaccines Against Influenza project (PI, Andrew Pekosz). The 

project's goal is to generate an influenza vaccine with activity against a 

variety of virus strains using the M2 protein. 

- NIAID issues a task order to Chiron Corporation for the production of 

an investigational H9N2 vaccine. Chiron will produce up to 40,000 

doses of vaccine with and without the MF59 adjuvant for clinical trials 

that will be conducted by NIAID, slated for 2005. 

- NIAID awards a grant to Innoject, Inc. (PI, Richard Gillespie) for the 

development of an auto-injector vaccine delivery system. Not only 

could the device be easy to use, but it could be broadly distributed in 

the event of an influenza pandemic. The clinical trial of the new delivery 

system, led by Dr. William Barr of Virginia Commonwealth University, 

will be conducted during the 2005-2006 flu season. 

 

- The Department of Health and Human Services (DHHS) issues the 

National Pandemic Influenza Preparedness Plan, designed to 

provide guidance to national, state, and local policy makers and health 

departments for public health preparation and response in the event of 

pandemic influenza outbreak. As outlined in Annex 10 of the Plan, the 

largest body of pandemic influenza research is supported by NIAID. 

 - DHHS issues a contract to Aventis Pasteur to manufacture and 

store two million doses of avian influenza H5N1 vaccine. 

 

- DHHS issues a contract to Sanofi Aventis Inc., to secure future 

egg supply for flu vaccines in the event of a pandemic flu outbreak or 

future vaccine shortages and to obtain initial investigational lots of 

pandemic influenza vaccines for clinical trials. 

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Recent Developments in NIAID Pandemic Influenza Research 

- NIAID awards a grant to Nexbio, Inc., to develop novel therapeutics 

for pandemic and epidemic flu (PI, Fang Fang). This novel class of 

fusion proteins may be capable of blocking infections by all strains of 

influenza viruses. 

- NIAID awards a grant to the Mount Sinai School of Medicine of NYU 

(PI, Adolfo Garcia-Sastre) for the molecular and biological 

characterization of the "Spanish Flu" to examine the reason behind 

the high lethality of the 1918 influenza pandemic. (Related Article) 

- NIAID awards a grant to the Wadsworth Center entitled "Discovery 

of a Novel Promoter in Pathogenic Influenza" (PI, David Wentworth) 

to further understand the molecular mechanisms of pathogenesis in 

avian influenza viruses. 

- NIAID awards a grant to St. Jude Children's Research Hospital to 

study combination chemotherapy for pandemic influenza (PI, 

Robert Webster) and test the hypothesis that combination therapy with 

two classes of anti-influenza drugs offers clinical and strategic 

advantages in the event of an influenza pandemic. 

- NIAID launches the Influenza Genome Sequencing Project that will 

put influenza sequence data rapidly in hands of scientists, enabling 

them to further study how influenza flu viruses evolve, spread, and 

cause disease and may ultimately lead to improved methods of 

detection, treatment, and prevention. This project is a collaborative 

effort among NIAID, NCBI/NLM, CDC, St. Jude Children's Research 

Hospital and others.(Sequencing Information) 

- NIAID issues a notice to the NIH Guide highlighting its interest in 

receiving grant applications focused on influenza research. 

- In January 2003, outbreaks of H5N1 in Asia were reported by the 

Global Health Organization. The outbreaks continued ongoing among 

bird populations in a number of Asian countries and human cases are 

reported in Thailand and Vietnam throughout early 2004. (WHO). In 

Canada, H7N3 infections in poultry workers in Canada are associated 

with an H7N3 outbreak among poultry in February. The H7N3-

associated illnesses consist of eye infections. (CDC). In Vietnam, a 16-

year-old girl in Vietnam is infected with H5N1 in December. The case 

coincides with several fresh poultry outbreaks reported in southern 

provinces. (WHO) 

2005 

- In early 2005, NIAID expands its Pandemic Preparedness in Asia 

contract to include surveillance activities in Vietnam, Thailand and 

Indonesia. 

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Recent Developments in NIAID Pandemic Influenza Research 

- In March, NIAID begins recruitment for a clinical trial to 

investigate the safety of an H5N1 avian influenza vaccine produced 

by sanofi-pasteur (formely Aventis Pasteur). Clinical sites, part of the 

NIAID VTEU network, will test the vaccine’s safety and ability to 

generate an immune response in 450 healthy adults. 

- In 2005, cases of H5N1 avian influenza are confirmed in Cambodia, 

Indonesia, Thailand, and Vietnam. By November 14th, 64 of 126 

confirmed cases have been fatal. (WHO) 

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