Clinical trial NCT00908323: Early Immune Responses to Vaccination - A Substudy to HVTN 205
Official title: Characterization of the Innate Immune Response to Candidate HIV Vaccines, an Ancillary Study to HVTN 205
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2009-05-25
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants enrolled in HVTN 205

Brief summary: HVTN 908 is a sub study of the HIV vaccine trial, HVTN 205. The purpose of this sub study is to better understand how a person's immune system responds to vaccines, particularly HIV vaccines. More specifically, researchers will determine whether early responses in the immune system help predict strong and long-lasting immunity.

Detailed description: Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not able to achieve their desired response. An alternative strategy to the antibody approach is the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were previously demonstrated to play an important role in the control of simian immunodeficiency virus (SIV), the HIV equivalent studied in rhesus macaque monkeys. Additionally, other studies suggest CTLs play an important role in viral control during chronic infection. Based on this information, several groups have shifted their focus to the development of CTL-based vaccines, some of which have entered advanced clinical trials.

A DNA/rMVA vaccine strategy is structured to bring about both T cell and antibody responses. The primary vaccination is DNA based and will express only HIV proteins as a way to produce an HIV-focused immune response. A secondary, rMVA boost vaccination, which expresses both HIV and MVA proteins will ideally amplify the focused response of the initial vaccination. The DNA and rMVA are physically two different vaccinations given at separate times but together they make up one preventive regimen. Both vaccine components express non-infectious virus-like particles.

The main study, HVTN 205 will evaluate the safety of and immune response to a two vaccine regimen in healthy, HIV-uninfected adults who never received an HIV preventive vaccine before. HVTN 205 will include two parts, Part A, in which the two vaccine regimen is compared to a placebo, and Part B, in which the two vaccine regimen will be compared to both a placebo and a single vaccine regimen with the rMVA vaccine.

HVTN 908 is a sub study of HVTN 205, and will explore the innate immune response to candidate HIV vaccines. In particular, researchers will study whether early immune response following vaccination can predict strong and long-lasting immunity. They will also study whether varying types of vaccines promote different immune responses soon after vaccination.

Only participants enrolled in HVTN 205 are eligible for HVTN 908. Approximately 50 participants will be recruited for the duration of 12 months per participant. The study will last for a total of 2 years, including enrollment, follow-up, and analysis. Potential participants of the sub study will undergo a screening visit before eligibility can be determined. Screening may involve a physical exam, health history, and blood tests.

There will be some additional visits for participants of HVTN 908 that are not included in the main study. Some main study visits may also take extra time for participants enrolled in the sub study. Blood samples will be taken at study visits. These samples are taken in addition to those for the main study.

Eligibility criteria: Inclusion Criteria:

* Scheduled receipt of a vaccine or placebo in HVTN 205
* For participants in Part B of HVTN 205, enrollment in HVTN 908 and HVTN 205 at the same time
* HVTN 908 assessment of understanding: completion of a questionnaire prior to enrollment; demonstration of understanding for all questionnaire items answered incorrectly.
* Body weight of 50 kg (110 lbs) or more
* Hemoglobin of 12.0 g/dL or more for female volunteers, and 13.0 g/dL or more for male volunteers
* Negative HIV-1 and -2 blood test

Exclusion Criteria:

* Clinically significant medical condition, physical examination finding, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion can be found in the study protocol.
* Any medical, psychiatric, or occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, or a participant's ability to give informed consent
* Pregnancy

Primary outcomes:
measure: Blood concentrations of lymphocyte populations, dendritic cells, monocytes, and granulocytes
timeFrame: Throughout study
measure: Serum concentrations of cytokines and chemokines
timeFrame: Throughout study
measure: Changes in PBMC gene expression relative to prevaccine levels of key genes expected to change, such as IP-10 and MCP-1
timeFrame: Throughout study
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: San Francisco
country: United States
facility: Bridge HIV CRS
state: California
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Erica Andersen-Nissen, PhD
role: STUDY_CHAIR
References:
citation: Baker BM, Block BL, Rothchild AC, Walker BD. Elite control of HIV infection: implications for vaccine design. Expert Opin Biol Ther. 2009 Jan;9(1):55-69. doi: 10.1517/14712590802571928.
citation: Browne EP, Littman DR. Myd88 is required for an antibody response to retroviral infection. PLoS Pathog. 2009 Feb;5(2):e1000298. doi: 10.1371/journal.ppat.1000298. Epub 2009 Feb 13.
citation: Zwolinska K. [Host genetic factors associated with susceptibility to HIV infection and progression of infection]. Postepy Hig Med Dosw (Online). 2009 Feb 24;63:73-91. Polish.