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Review
. 2017 Jan;275(1):271-284.
doi: 10.1111/imr.12510.

Survivors Remorse: antibody-mediated protection against HIV-1

George K Lewis  1 , Marzena Pazgier  1 , Anthony L DeVico  1
Affiliations
Review

Survivors Remorse: antibody-mediated protection against HIV-1

George K Lewis et al. Immunol Rev. 2017 Jan.

Abstract

It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non-human primate (NHP) studies as well as the RV144 vaccine trial indicate that non-neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible.

Keywords: AIDS vaccine; HIV-1; neutralizing antibodies; non-neutralizing antibodies.

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Conflict of interest statement

CONFLICTS OF INTEREST

Drs. Lewis and DeVico own shares in Profectus Biosciences. This conflict is managed by the University of Maryland Baltimore pursuant to state and federal laws.

Figures

FIGURE 1
FIGURE 1
Entropy plot for gp120 illustrating conserved and variable regions. The individual entropy values are shown indicating the per-residue protein sequence variability and the curve was generated as a moving average to depict the relative regional diversity
FIGURE 2
FIGURE 2
Depiction of the relative sequence variability on a model of CD4-triggered gp120. Blue represents the highest protein sequence conservation, whereas red represents the highest protein sequence variability
FIGURE 3
FIGURE 3
Logo plots for the per-residue protein sequence variation in the C1 region. The rectangles represent contact residues for the A32-subregion of Epitope Cluster A. For brevity, the C2 contact residues for the A32-subregion are not shown but they are equally conserved as those of the C1 region
See this image and copyright information in PMC

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