June 5, 2017

New Studies Improve Candidate Vaccine Design for HIV Subtypes Most Common in India and Africa

IAVI scientists demonstrate how to produce a variety of HIV surface protein variants.

Two papers published recently in the journal Immunity provide important information to inform HIV vaccine design. Using cutting-edge tools, scientists with the International AIDS Vaccine Initiative’s Neutralizing Antibody Center (IAVI NAC) at The Scripps Research Institute describe the first successful attempt at obtaining a high-resolution snapshot of a subtype C outer envelope or protein “spike” that decorates the surface of the virus. Until now, researchers have only been able to do so for subtypes A, B, and G. In the second study, researchers isolate and analyze neutralizing antibodies that are generated following vaccination of non-human primates (monkeys) with these vaccine candidates, which can penetrate these well-shielded spikes.

“Together the two studies show how structure-based immunogen design can advance vaccine development for HIV, and potentially other infectious diseases,” said Richard Wyatt, Director of Viral Immunology at the IAVI NAC. “Through enhanced understanding of subtype C’s structural complexities, we understand how antibodies can penetrate HIV’s dense protective armor – a camouflaging sugar shield – to target and latch onto a surface region called V2 that possesses some conserved sites.” Targeting of V2 also was seen in human volunteers in the RV144 – the Thai trial – the only HIV vaccine clinical trial to date to show any effectiveness.

Seeking a more effective vaccine, IAVI’s scientists generated a stabilized version of the envelope protein from a subtype C virus isolated previously from an HIV-infected Indian individual and generated crystals that permitted the determination of its atomic structure. They arranged these envelope spikes on the outside of nanoparticles, and injected the spiked nanoparticles into monkeys. Subsequent analysis showed that the vaccinated monkeys mounted immune defenses, including B-cell responses and HIV antibodies capable of blocking this subtype C HIV strain virus. The monkeys’ immune response is one indication that an HIV vaccine may be developed from this initial immunogen design approach, perhaps using many spikes derived from multiple strains to accommodate viral diversity.

Wyatt’s findings are important for several reasons. Subtype C HIV strains are responsible for the majority of HIV-1 infections worldwide and the findings presented in these two studies define a roadmap to produce vaccines for subtype C HIV viral variants. Also, the identification of which regions are immunogenic on these envelope glycoprotein immunogens, that is which elements stimulate neutralizing antibodies, inform future vaccine re-design efforts.

These findings further inform future clinical trials toward a vaccine that can prevent infection with multiple strains of HIV – otherwise known as a “broadly effective” vaccine.

Read more from Scripps here.