Optimized immunizations reliably elicit protective antibodies in preclinical study, marking an important milestone on the way to an effective HIV vaccine.

For decades, HIV has successfully evaded all efforts to create an effective vaccine but researchers at The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) are steadily inching closer. Their latest study, published in the current issue of the journal Immunity, demonstrates that optimizing the mode and timing of vaccine delivery is crucial to inducing a protective immune response in a preclinical model.

More than any other factors, administering the vaccine candidate subcutaneously and increasing the time intervals between immunizations improved the efficacy of the experimental vaccine and reliably induced neutralizing antibodies. Neutralizing antibodies are a key component of an effective immune response. They latch onto and inactive invading viruses before they can gain a foothold in the body and have been notoriously difficult to generate for HIV.

“This study is an important staging point on the long journey toward an HIV vaccine,” says TSRI Professor Dennis R. Burton, PhD, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI–ID) at TSRI. “The vaccine candidates we worked with here are probably the most promising prototypes out there, and one will go into people in 2018,” says Burton.

“There had been a lot of big question marks and this study was designed to get as many answers as possible before we go into human clinical trials,” adds senior co–author Shane Crotty, PhD, a professor in LJI’s Division of Vaccine Discovery. “We are confident that our results will be predictive going forward.”

HIV has faded from the headlines, mainly because the development of antiretroviral drugs has turned AIDS into a chronic, manageable disease. Yet, only about half of the roughly 36.7 million people currently infected with HIV worldwide are able to get the medicines they need to control the virus.

At the same time, the rate of new infections has remained stubbornly high, emphasizing the need for a preventive vaccine.

The latest findings are the culmination of years of collaborative and painstaking research by a dozen research teams centered around the development, improvement, and study of artificial protein trimers that faithfully mimic a protein spike found on the viral surface. At the core of this effort is the CHAVI–ID immunogen working group.

The recombinant trimers, or SOSIPs as they are called, were unreliable in earlier, smaller studies conducted in non–human primates. Non–human primates, and especially rhesus macaques, are considered the most appropriate pre–clinical model for HIV vaccine studies, because their immune system most closely resembles that of humans.

The study is titled, “Elicitation of robust Tier 2 neutralizing antibody responses in non–human primates by HIV envelope trimer immunization using optimized approaches.”