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SIV infection duration largely determines broadening of neutralizing antibody response in macaques
Fan Wu, … , David Montefiori, Vanessa M. Hirsch
Fan Wu, … , David Montefiori, Vanessa M. Hirsch
Published July 14, 2020
Citation Information: J Clin Invest. 2020;130(10):5413-5424. https://doi.org/10.1172/JCI139123.
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Research Article AIDS/HIV Virology Article has an altmetric score of 3

SIV infection duration largely determines broadening of neutralizing antibody response in macaques

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Abstract

The development of broadly neutralizing antibodies (BNAbs) in HIV infection is a result of long-term coevolutionary interaction between viruses and antibodies. Understanding how this interaction promotes the increase of neutralization breadth during infection will improve the way in which AIDS vaccine strategies are designed. In this paper, we used SIV-infected rhesus macaques as a model to study the development of neutralization breadth by infecting rhesus macaques with longitudinal NAb escape variants and evaluating the kinetics of NAb response and viral evolution. We found that the infected macaques developed a stepwise NAb response against escape variants and increased neutralization breadth during the course of infection. Furthermore, the increase of neutralization breadth correlated with the duration of infection but was independent of properties of the inoculum, viral loads, or viral diversity during infection. These results imply that the duration of infection was the main factor driving the development of BNAbs. These data suggest the importance of novel immunization strategies to induce effective NAb response against HIV infection by mimicking long-term infection.

Authors

Fan Wu, Ilnour Ourmanov, Andrea Kirmaier, Sivan Leviyang, Celia LaBranche, Jinghe Huang, Sonya Whitted, Kenta Matsuda, David Montefiori, Vanessa M. Hirsch

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Figure 5

Sequence divergence and diversity of viral Env in macaques infected with the 3 clones.

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Sequence divergence and diversity of viral Env in macaques infected with...
(A) Codons that distinguish the 3 inoculated SIVsmE660 variants in C1 (34–73; top left), V1 (113–154; top right), V2 (154–194; bottom left), and V4 (405–440; bottom right) regions evolved toward the tier 3 viral sequence correlated with the appearance of NAbs in the macaques. Sequence logos that were generated based on the diversity of viral sequences at different time points in the group of macaques are shown. (B) The dynamics of Env diversity (upper) and divergence (lower) at C1, V1, V4, and the Gp41 tail across the 3 tiers are shown. Diversity was calculated as the average number of amino acid differences among the pooled sequences in each sample. Divergence was calculated as the average number of amino acid differences between the sampled sequence and the inoculated reference. (C) The difference between Env divergence and diversity was calculated by subtracting the diversity number from the divergence number.

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