$13 Million for AIDS Vaccine Research

$13 million in grants for developing an effective vaccine for HIV/AIDS.

By Holly Korschun, Woodruff Health Sciences Center

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Bali Pulendran PhD

A team of researchers at Emory University has received a three-year grant of $6 million from the Bill & Melinda Gates Foundation as part of a worldwide effort aimed at developing an effective vaccine for HIV/AIDS.

The grant is part of the Collaboration for AIDS Vaccine Discovery (CAVD), an international network of scientists and experts dedicated to designing a variety of novel HIV vaccine candidates and advancing the most promising candidates to clinical trials. Bali Pulendran PhD, principal investigator of the grant, will lead the Emory team, which comprises researchers from Yerkes National Primate Research Center and the Emory Vaccine Center. Rafi Ahmed PhD, director of the Vaccine Center, is co-principal investigator.

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Rafi Ahmed PhD

The Emory researchers will lead a project in nonhuman primates aimed at programming innate immunity to induce optimally effective protective antibodies against HIV. They will use vaccine technology Pulendran and his Emory colleague Sudhir Kasturi PhD, developed. They created nanoparticles that mimic viruses and are covered with molecules that activate Toll-like receptors (TLRs). In mice, these particles can stimulate long-lasting immune responses to inactivated influenza virus that last the lifetime of the animal. The nanoparticles were also shown to have effective immunity against influenza in nonhuman primates; this research was reported in the February 23, 2011, online issue of Nature.

The grant from the Gates Foundation will allow the researchers to optimize their TLR nanoparticle approach for an HIV vaccine and test the vaccine’s ability to provide immune protection in a nonhuman primate model of HIV infection. 

"An intriguing aspect of the data from the recent vaccine clinical trial in Thailand, RV144, was that although it resulted in a modest reduction in infection compared with placebo, protective immunity diminished over time," notes Pulendran. "This underscores the importance of generating durable antibody responses. We believe our approach is particularly well-suited to this challenge." 

In addition to Bali Pulendran, Charles Howard Candler Professor of Pathology and Laboratory Medicine at Emory School of Medicine and a leading researcher at Yerkes, and Rafi Ahmed, a Georgia Research Alliance Eminent Scholar, the Emory team includes Sudhir Kasturi, research assistant professor at Yerkes; Francois Villinger PhD, chief of the division of pathology and laboratory medicine at Yerkes; and Tianwei Yu PhD, assistant professor of biostatistics at Rollins School of Public Health, Emory University. The Emory researchers also are investigators in the Emory Center for AIDS Research (CFAR). 

Other investigators are Shane Crotty PhD, La Jolla Institute for Allergy and Infectious Diseases, and Jeffrey Hubbell and Melody Swartz, bioengineers at Ecole Polytechnique Federale de Lausanne (EPFL) and investigators at 3M Pharmaceuticals and Novartis. 

The Bill & Melinda Gates Foundation launched the CAVD in July 2006 and has since funded a total of 30 grants supporting investigators in 19 countries. The CAVD operates on the principle that accelerating progress toward an AIDS vaccine requires the creativity of individual investigators supported by a collaborative approach that emphasizes the sharing of scientific information and the standardization of laboratory techniques and data analysis. 

Emory Vaccine Center receives $7 million from NIH in major HIV/AIDS focus  

A seven-year initiative funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), will focus an intensive national effort on developing a vaccine against HIV and AIDS. Emory University will receive approximately $7 million for its part of the project. 

The new Centers for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID), funded by a projected total of $186 million, will be directed by the Scripps Research Institute and Duke University. Supporting the Scripps Research Institute will be primary scientific leaders at Emory, the Rockefeller University/Howard Hughes Medical Institute, and the Ragon Institute. 

Rafi Ahmed PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, will lead Emory’s project and will collaborate with Bali Pulendran PhD, Emory professor of pathology and laboratory medicine and a researcher at the Yerkes National Primate Research Center, and Guido Silvestri, chief of microbiology and immunology at Yerkes and a Georgia Research Alliance Eminent Scholar. All are members of the Emory Center for AIDS Research. 

The goal of CHAVI-ID is to accelerate HIV vaccine development by supporting multidisciplinary research into immune responses that prevent or contain HIV infection and by generating model vaccine components that can induce these protective immune responses. 

"Despite the development of lifesaving drugs, the HIV/AIDS epidemic still remains a tremendous challenge, with 34 million infected individuals throughout the world. Our greatest hope for stopping this disease remains an effective vaccine," says Ahmed. "The intensive approach of CHAVI-ID will give us an excellent chance of accomplishing that."

In the Scripps-led component of CHAVI-ID, researchers at Scripps and the Rockefeller Institute will lead the project’s first focus, centering on B cell and antibody studies. The second focus, led by Ahmed, along with Bruce Walker, PhD, at the Ragon Institute and colleagues at the La Jolla Institute of Allergy and Immunology, will center on CD4+ T cell studies.

A successful HIV vaccine needs to elicit protective antibodies, but the development of most neutralizing antibody responses is dependent on CD4+ T cells, with control by follicular helper CD4+ T (Tfh) cells.

In the Emory project, Ahmed and Pulendran will work together to understand the mechanisms of Tfh cell generation after immunization with HIV envelope (ENV) proteins and to identify adjuvants that can enhance these T helper cells and also induce potent responses by B cells (antibody-producing cells). Their work will include a powerful nanoparticle vaccine approach that was pioneered in Pulendran’s laboratory. Silvestri will perform immunization studies in nonhuman primates at Yerkes to further define the complex immune response to the HIV virus and to potential vaccine components.

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