HIV Vaccine Research and Development Researchshot2

Researchers within the program draw on the military medical community's vast experience and expertise in vaccine research. Program scientists leverage these skills to develop effective vaccines that will not only protect U.S. troops from infection, but also bring under control the international proliferation of HIV.

MHRP engages in basic research to support HIV vaccine development. Efforts include:

* pre-clinical basic immunology and vaccinology
* molecular biology
* pre-clinical vaccine evaluation in animal and laboratory models

Researchers acquire or develop methods to assess the immunologic evidence of vaccine performance and surrogate markers of protective immunity in HIV disease. The assays are implemented in full cGLP (current Good Laboratory Practices) compliance to ensure reproducibility and robustness of generated data. The projects under this task involve the establishment and diversification of multiple panels of reagents, including large panels of primary HIV-1 isolates and serum/plasma pools from international sites for use in vaccine development and immunogenicity assays, or for use as components of vaccine candidates.

Immunogenicity testing of potential vaccine constructs is evaluated in a fully compliant GLP setting. The preclinical evaluation of candidate vaccines facilitates the down-selection, and advancement to the clinic, of novel HIV envelope subunit vaccines that elicit promising antibodies in early studies.
Vaccine Challenges

There are many barriers to developing an effective vaccine to prevent HIV. No vaccines currently induce broadly reactive and potent neutralizing antibodies against circulating strains of HIV, and there is no consensus as to which biomarkers correlate with protection from disease acquisition or progression. To overcome these obstacles, program researchers are taking a multifaceted approach to vaccine development.
Phase III Trial in Thailand

On September 24, 2009 the U.S. Army Surgeon General announced the results of a study that showed an investigational HIV vaccine regimen was safe and, for the first time, modestly effective in preventing HIV infection. It lowered the rate of HIV infection by 31.2% in a Phase III clinical trial involving more than 16,000 adult volunteers in Thailand.

Although the efficacy is modest, this study represents a major scientific achievement that has important implications for HIV vaccine testing and development. MHRP provided study leadership, and is currently developing follow-up scientific plans in collaboration with outside experts.
DNA/MVA HIV Vaccine

Program researchers are pursuing a prime-boost combination of DNA and an attenuated viral vector—modified vaccinia Ankara (MVA)—to deliver HIV proteins to antigen-presenting cells. Safety is an overriding factor when it comes to choosing vectors. MVA is a modified version of the smallpox vaccine that has been used safely and effectively to eradicate that disease world-wide. Both ours and other MVA products have been shown to safe and immunogenic in numerous Phase I and II clinical trials. The DNA prime has also been safely administered alone and in combination with MVA and other candidate vaccines.

Studies with the MHRP DNA/MVA HIV vaccine are planned for 2009 in the U.S., Thailand and East Africa.

A number of collaborative studies using components of our vaccine are already underway. The Karolinska Institute is currently conducting a Phase I trial (HIVIS03, n=60) in Tanzania testing a prime-boost HIV vaccine regimen using unadjuvanted DNA vaccines followed by a viral vector vaccine. The boost vaccine component, based on Modified Vaccinia Ankara, was developed by MHRP. This HIV vaccine research study is being conducted in collaboration with Muhimbili University (MUHAS).
Phase I/II Clinical Trial

Program sites in East Africa are in the follow-up stages in a study testing the NIAID Vaccine Research Center HIV vaccine consisting of a DNA prime and recombinant Adenovirus type 5 boost. The study, known as MHRP: RV 172 enrolled 326 participants in Uganda, Tanzania and Kenya. The vaccine was highly immunogenic and well tolerated.