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Viruses 2018, 10(5), 262; https://doi.org/10.3390/v10050262

Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques

1
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA
2
School of Medicine, New York University, New York, NY 10016, USA
*
Author to whom correspondence should be addressed.
Received: 23 April 2018 / Revised: 11 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue HIV Vaccines)
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Abstract

Simian-human immunodeficiency virus (SHIV) infection provides a relevant animal model to study HIV-1 neutralization breadth. With previously identified SHIVSF162P3N infected rhesus macaques that did or did not develop neutralization breadth, we characterized the transmitted/founder viruses and initial autologous/homologous neutralizing antibodies in these animals. The plasma viral load and blood CD4 count did not distinguish macaques with and without breadth, and only one tested homologous envelope clone revealed a trend for macaques with breadth to favor an early homologous response. In two macaques with breadth, GB40 and FF69, infected with uncloned SHIVSF162P3N, multiple viral variants were transmitted, and the transmitted variants were not equal in neutralization sensitivity. The targets of initial autologous neutralizing antibodies, arising between 10 and 20 weeks post infection, were mapped to N462 glycan and G460a in gp120 V5 in GB40 and FF69, respectively. Although it is unclear whether these targets are related to later neutralization breadth development, the G460a target but not N462 glycan appeared more common in macaques with breadth than those without. Longitudinal plasmas revealed 2–3 sequential waves of neutralizing antibodies in macaques with breadth, implicating that 3 sequential envelope variants, if not more, may be required for the broadening of HIV-1 neutralizing antibodies. View Full-Text
Keywords: HIV vaccine; SHIV; rhesus macaque; neutralizing antibody HIV vaccine; SHIV; rhesus macaque; neutralizing antibody
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Jia, M.; Lu, H.; Kong, X.-P.; Cheng-Mayer, C.; Wu, X. Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques. Viruses 2018, 10, 262.

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