U.S. Military HIV Research Program (USMHRP) researcher Victoria R. Polonis, Ph.D., and colleagues released findings on a study of cross-clade neutralization patterns among HIV-1 strains from six major clades in the 5 Jun 2008 issue of Virology.
Broadly neutralizing antibodies are likely to play a key role in any successful global vaccine for HIV. This study looked specifically at the role of clade in eliciting protective responses. Working with USMHRP colleague Francine McCuthan, Ph.D., researchers had access to a wide range of pure clade reagents, which they used to analyze the cross-clade neutralization patterns.
Another key goal of this study was to assess the impact of assay choice on the evaluation of cross-clade neutralization. The team examined the performance of different types of antibodies in both traditional primary cell neutralization assays and the newer, more standardized TZM-bl reporter cell line assays.
A major finding of the study was that the results of the two assay formats showed no direct correlation. This underscores the need to identify a physiologically relevant and standardized platform for reproducible measurement of neutralizing antibodies. Until such a product is available, researchers recommend that parallel evaluation with both platforms should be contemplated until a better understanding of immune correlates of protection is achieved.
Polonis and colleagues also found that the clade C antibody pool (from subjects infected with clade C from Tanzania) was broadly cross-reactive, neutralizing the greatest number of viruses in both assays. "The data is encouraging," noted Polonis. "Clade C vaccine products certainly warrant further investigation in light of several recent publications regarding potentially novel properties of the C envelope and because more than half of the global HIV-1 infections are clade C." In fact, Polonis and her team have an ongoing project to develop a clade C envelope subunit vaccine derived from acute infection.
Prior to acceptance for publication, this data was presented by Dr. Polonis at The Global Workshop on HIV Neutralization in Varese, Italy (March 2007), at The Enterprise Workshop on Antibodies in HIV Vaccine Development in Reston, VA (May 2007), at a special seminar for the Division of AIDS, NIH (June 2007), and by Dr. Bruce Brown at AIDS Vaccine 2007 in Seattle, WA (Aug 2007). The publication was also cited and discussed in the July 9 issue of Vaccine Weekly.
This work was funded by the Military Infectious Disease Research Program (MIDRP); in addition, Dr. Polonis' group is part of the Vaccine Immune Monitoring Consortium (VIMC) centered at Duke University. These highly collaborative Vaccine Consortia were endorsed by the GHAVE (the Global HIV/AIDS Vaccine Enterprise) and funded by the Bill and Melinda Gates Foundation.
The U.S. Military HIV Research Program (USMHRP) is at the forefront of the battle against HIV/AIDS to protect U.S. troops from infection and to reduce the global impact of the disease.
USMHRP is a multi-disciplinary effort headed by the Walter Reed Army Institute of Research in conjunction with the U.S. Army Medical Research and Material Command and the Henry M. Jackson Foundation for the Advancement of Military Medicine.
While its primary focus has been on developing a globally effective preventive HIV-1 vaccine, USMHRP is actively committed to and engaged in providing effective prevention, care and treatment programs in the communities in which they conduct research. At these sites—which include Tanzania, Uganda, Kenya, Nigeria and Thailand — they also focus on strain surveillance, cohort development and therapeutic studies.
For more information, visit www.hivresearch.org.
Journal
Virology