Findings on immune response inform direction of HIV vaccine development

SEATTLE – Oct. 21, 2015 – Research conducted in the past few years is shedding light on the role the immune response to vaccines plays in offering protection from HIV, information that is helping shape the way forward in developing a new HIV vaccine.

In 2009, results of the landmark RV144 HIV vaccine trial conducted in Thailand were announced: Vaccine recipients had a 31 percent reduction in HIV infection. The study was widely considered a turning point in HIV vaccine research because it marked the first time an experimental vaccine showed any protection against HIV. Shortly after the results were announced, an international research consortium was launched to look at whether specific immune responses associated with protection could be defined and provide a road map to further increase the efficacy of RV144. 

A review article published today (Oct. 21) in Science Translational Medicine looks at findings gleaned in the past four years describing types of immune responses that a preventive HIV vaccine may need to achieve protection against acquiring  HIV infection.

Dr. Larry Corey, a leading virologist and the founder and current co-principal investigator of the Fred Hutchinson Cancer Research Center-based HIV Vaccine Trials Network, is the first author on the paper, titled “Immune correlates of vaccine protection against HIV-1 acquisition.”

Other co-authors include Fred Hutch statistician Dr. Peter Gilbert and vaccine researchers Drs. Georgia Tomaras and Barton Haynes of Duke University Medical Center; Dr. Giuseppe Pantaleo of Lausanne University Hospital and Swiss Vaccine Research Institute;  and Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.

Recent years “have seen an unprecedented scientific effort that has provided a wealth of new information on the immune responses that are potentially associated with and responsible for protection against HIV acquisition,” the authors wrote.

Analyses of RV144 volunteers revealed that those who developed a unique set of vaccine-induced  antibodies in combination  with a high level of  CD4 T-cell  responses  to  the outer portion of the  HIV virus,  called  its envelope gene, correlated with reduced HIV infection.  One of the surprises in these findings is that these antibodies did not neutralize the virus in classical test tube-like assays yet still were  able to  put  pressure on  potential infecting   viruses.

Understanding such “correlates of protection” is critical to the ultimate development of an HIV vaccine effective enough to bring to the public.  Defining the immune signature of protection helps researchers screen new candidate vaccines faster by allowing the selection of vaccine regimens that enhance these responses. 

The HIV Vaccine Trials Network is conducting a clinical trial now in South Africa to test a modified version of the Thai vaccine regimen that has been altered with the aim of making it more protective as well as longer-lasting. If the regimen induces the predicted immune system response, the next phase will be a larger trial beginning in late 2016 or early 2017 to test for efficacy, or whether the vaccine actually protects those who receive it from being infected with HIV. The HVTN 100 trial and related studies are part of the Pox-Protein Public-Private Partnership, or P5, the international consortium formed to follow up on the results of RV144.

Researchers continue to build on these findings as well as to investigate other strategies, including developing vaccines to elicit production of antibodies that are broadly neutralizing against a variety of HIV strains.

Data from the recent research provides hypotheses and new benchmarks as work goes forward to build on the efficacy of the RV144 vaccine. “Whether increased (vaccine efficacy) will be achieved by these efforts remains to be determined,” the authors wrote. “However this collaborative effort has produced a momentum and series of immune targets that will hopefully lead to an effective global vaccine effort.” 

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At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS, and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.