Discovery medicine trials are underway to evaluate several HIV vaccine immunogens designed to prime the immune system to make broadly neutralizing antibodies. What comes next?
For several years now, researchers have been engineering HIV vaccine immunogens that can stimulate the immune system to do something it rarely accomplishes on its own — generating antibodies that can effectively neutralize most, if not all, HIV variants in circulation. These so-called broadly neutralizing antibodies (bnAbs) are considered the linchpin of an effective vaccine but inducing them is a monumental task.
For starters, they develop only occasionally in people living with HIV, and only after years of exposure to an ever-evolving virus. And, when these bnAbs do appear, they have many unusual properties — they are extensively mutated, for example — which make them difficult to induce through vaccination.
As a result, scientists have had to develop new ways to train, or, more accurately, coax the immune system to generate bnAbs. This requires a stepwise process. The first step is to engineer vaccine immunogens capable of priming the immune system. The goal of these priming immunogens is to engage specific subsets of naïve B cells that have the capacity to make bnAbs.
Results from early-stage discovery medicine trials show that several vaccine immunogens in development successfully initiate this process of bnAb development. Now, researchers must design subsequent immunogens to boost these responses and coax these B cells along the maturation pathway.
This work is being guided by detailed molecular, functional, and structural analyses of B-cell and antibody responses induced by the priming immunogens. These analyses were the subject of the workshop “B Cell Immune Repertoire Analysis for HIV Vaccines,” held by the U.S. National Institute of Allergy and Infectious Diseases’ (NIAID) Division of AIDS on August 13, 2024. At the virtual meeting, HIV vaccine experts reviewed clinical data for some of the most advanced immunogens. They also described the complex and labor-intensive methods used to characterize the immune responses these immunogens induce and brainstormed ways to make these processes more efficient and cost-effective, all while maximizing the amount of data collected. Fine-tuning these processes will become even more important as sequential vaccination regimens advance into iterative trials using platforms such as mRNA.
Read the full report form the workshop here.
Source : IAVI
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