Sequential Immunizations May Be Needed for Successful HIV Vaccination

July 25, 2015

Vaccination to prevent HIV infection may require sequential immunizations targeted to specific stages of immune response, according to the results of a study in mice. The initial antigen would spur B cells to start making the right kind of antibodies, while the subsequent antigen would help those antibodies mature into forms that would block HIV infection.

Intense research for 25 years has failed to yield a vaccine that will protect a high proportion of people from HIV. Some of the failed candidates used a two-step prime-boost strategy, but new work from The Rockefeller University and collaborating institutions suggests a different step-by-step process aimed at producing broadly neutralizing antibodies (bNAbs) to parry HIV. Without help from a vaccine, some HIV-positive people generate bNAbs over the course of several years as their B cells mutate to counter their HIV. bNAbs are "broad" because they can bind to and neutralize diverse HIV strains. Making a vaccine that coaxes forth bNAbs has become a prime goal of vaccine research, but one that remains elusive.

Now, work by the Rockefeller team and collaborators suggests what it will take to produce bNAbs in an HIV-negative person: at least two (and possibly more) immunizations with different goals administered over a span of time.

The study involved two groups of mice genetically manipulated to produce human-like antibodies. The first mouse group had no antibodies that target HIV; it represented a B-cell response early in the course of HIV infection, before B cells have evolved to produce bNAbs. The second mouse group had antibodies mutated in a way that should lead to bNAb development; it represented the immune system at a later stage of infection.

The researchers exposed both groups of mice to two antigens: the first engineered to make the highly conserved binding site on CD4+ T cells accessible to antibodies, and the second designed to resemble the natural antigen seen in HIV infection. In the early-stage mice, the engineered antigen prodded B cells that can serve as bNAb precursors to diversify and spew antibodies resembling those at an early stage of bNAb production. In the later-stage mice, the more natural antigen nudged mice to make antibodies that could neutralize a broader array of HIV strains.

"While our results suggest sequential immunizations may make it possible to vaccinate against HIV, we have only just begun to understand how this sequence would work," cautioned Rockefeller postdoctoral fellow Pia Dosenovic in a press statement. "We know the beginning and the end, but we don't know what should happen in the middle."

Mark Mascolini is a freelance writer focused on HIV infection.

Copyright © 2015 Remedy Health Media, LLC. All rights reserved.


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