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Review
. 2019 Jul 25;7(3):74.
doi: 10.3390/vaccines7030074.

Impact of HIV-1 Diversity on Its Sensitivity to Neutralization

Karl Stefic  1   2 , Mélanie Bouvin-Pley  3 , Martine Braibant  4 , Francis Barin  4   5
Affiliations
Review

Impact of HIV-1 Diversity on Its Sensitivity to Neutralization

Karl Stefic et al. Vaccines (Basel). .

Abstract

The HIV-1 pandemic remains a major burden on global public health and a vaccine to prevent HIV-1 infection is highly desirable but has not yet been developed. Among the many roadblocks to achieve this goal, the high antigenic diversity of the HIV-1 envelope protein (Env) is one of the most important and challenging to overcome. The recent development of broadly neutralizing antibodies has considerably improved our knowledge on Env structure and its interplay with neutralizing antibodies. This review aims at highlighting how the genetic diversity of HIV-1 thwarts current, and possibly future, vaccine developments. We will focus on the impact of HIV-1 Env diversification on the sensitivity to neutralizing antibodies and the repercussions of this continuous process at a population level.

Keywords: HIV-1 vaccine; broadly neutralizing antibodies; diversity; envelope; evolution.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sites of vulnerability on the HIV-1 envelope (Env) trimer and broadly neutralizing antibodies (bnAb) classes.
Figure 2
Figure 2
HIV-1 genetic diversity impacts its susceptibility to bnAbs. As an illustration, neutralization data were gathered for four bnAbs (PGT121, PG9, 3BNC117, and 10E8), each targeting a different site of vulnerability (V3g, V1V2g, CD4bs, and MPER, respectively), tested against three panels of transmitted-founder (T/F) viruses representing clade C (n = 200) [60], B (n = 40) [62], and CRF02_AG (n = 33) [61]. Based on individual half-maximal inhibitory concentration (IC50) values, the percentage of viruses neutralized at the bnAb concentration of 1 μg/mL within each clade is represented and highlights intersubtype discrepancies of the neutralization coverage.
Figure 3
Figure 3
Schematic representation depicting the co-evolution between the virus and NAbs in an HIV-1 infected individual. (Top): Among a diverse population of variants from the transmitter, only a single variant (red) is sexually transmitted to the receiver in most of the cases. It gives rise to autologous NAbs (red) that exert a selective pressure. An escape variant becomes predominant (green), which induces, in turn, a specific autologous neutralizing response, and so on as the phenomenon continues. Progressively, this evolution at the individual level has a repercussion on the diversification of the HIV-1 species leading to an increasing resistance to NAbs at the population level (bottom).
Figure 4
Figure 4
The diversification of HIV-1 over the course of the epidemic is associated with increased resistance to bnAbs. Panels (A–D) illustrate this phenomenon for two subtypes, by studying T/F viruses sampled shortly after seroconversion in HIV-1 infected individuals from 1987 to 2012 in France [61,62,73]. (A,B) The genetic distance of subtype B (A) and CRF02_AG (B) T/F variants from a consensus B or CRF02_AG, respectively, correlates with calendar year and increases over time. Sequences were codon-aligned with CRF02_AG consensus sequence (Los Alamos database). After exclusion of hypervariable regions, evolutionary divergence was estimated by distance matrix using MEGA software. Pearson correlation. (C,D) IC50 values of 3BNC117 were positively correlated with distance, indicating an increase in resistance. Spearman correlation.
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