Identifying new ‘template’ for potent vaccine against HIV

Electromicrograph showing an HIV-infected T cell in blue and yellow
Scientists aim to reproduce the broadly neutralizing antibody response against a vulnerable HIV target in future HIV design. (NIAID)

Development of an effective HIV vaccine faces many challenges not seen in other prophylaxis efforts. The virus mutates like crazy, and it knows how to cloak itself to evade our immune system, just to name two. Now, scientists at the International AIDS Vaccine Initiative (IAVI) and the Scripps Research Institute have identified certain viral changes and antibody features that could provide a possible template for vaccine design that tackles both issues.

Years after an HIV infection, some people self-produce powerful broadly neutralizing antibodies (bnAbs) that can block HIV from infecting immune cells. Though the natural process happens too late to protect these people from being infected, understanding this mechanism can help guide vaccine development. And that’s the rationale behind a study led by Elise Landais, Ph.D., a senior research scientist with IAVI, and published in Immunity.

“HIV mutates 1000 times more than influenza, if not more. With HIV, even within one individual, you have an amazing diversity of strains,” Landais said in an emailed interview with FierceBiotechResearch. “We see how difficult it is to develop a flu vaccine that targets the correct strain for that year, let alone one that can cover all strains.”

The other challenge, the so-called glycan shield, could hide virus target areas from HIV antibodies, and the shield itself is immunosilent, meaning that the immune system couldn’t tell it apart from sugars on our own proteins, Landais explained.

Through an ongoing epidemiological study in several African countries dubbed Protocol C, Landais’ team looked at people whose immune systems were able to tackle both the diversity and glycan issues during natural infection. From about 600 volunteers with HIV infection enrolled in the study, researchers identified an individual who developed bnAbs targeting the V2 apex site on HIV’s surface. The V2 apex is a recently identified “site of vulnerability” where bnAbs can work most efficiently, blocking the majority of HIV strains.

“We want to reproduce this process with a vaccine but to do it quicker than the human body, which takes years to develop bnAbs,” Landais said. “To do so we need to understand how these exceptional antibodies ‘learned’ to deal with the HIV glycan shield and variability in these unique individuals.”

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Using a technique called next-generation sequencing, these researchers traced bnAb development back to the beginning and identified both viral variations and antibody structural features critical for V2 apex bnAb development. It is also reassuring for scientists that the viral features are very similar to those found in another study’s volunteer who developed the same type of V2 apex bnAb responses.

Landais said the new findings, combined with previous work, “could offer a possible template for vaccine design,” but cautioned that more data from individuals are needed to create a clearer road map.

First thing moving forward, a group of scientists led by William Schief, Ph.D., an HIV researcher at the Scripps Research Institute, will take this information and try to design immunogens that teach the immune system to develop the same type of HIV bnAbs that target the V2 apex.