Envelope-specific B-cell populations in African green monkeys chronically infected with simian immunodeficiency virus

Ruijun Zhang,David R Martinez,Christina Stolarchuk,Jessica Wasserscheid,Lisa Colvin,Sallie R Permar,Minyue Wang,Guido Ferrari,Ashley M Trama,Nikoleta Juretic,Robert Parks,Trina Arifin,Jonathon E Himes,Justin Pollara,Nathan Vandergrift,Ken Dewar,Andrew Foulger,Hua‐Xin Liao ,Quoc‐Hung Nguyen ,R Whitney Edwards ,Josh D Amos

doi:10.1038/ncomms12131

Abstract

African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV). Interestingly, features of the envelope-specific antibody responses in SIV-infected AGMs are distinct from that of HIV-infected humans and SIV-infected rhesus monkeys, including gp120-focused responses and rapid development of autologous neutralization. Yet, the lack of genetic tools to evaluate B-cell lineages hinders potential use of this unique non-human primate model for HIV vaccine development. Here we define features of the AGM Ig loci and compare the proportion of Env-specific memory B-cell populations to that of HIV-infected humans and SIV-infected rhesus monkeys. AGMs appear to have a higher proportion of Env-specific memory B cells that are mainly gp120 directed. Furthermore, AGM gp120-specific monoclonal antibodies display robust antibody-dependent cellular cytotoxicity and CD4-dependent virion capture activity. Our results support the use of AGMs to model induction of functional gp120-specific antibodies by HIV vaccine strategies.

Highlights

African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV)
As we found that the VH and VL genes of AGM are closer to those of rhesus monkeys (RMs) than to those of humans, AGM VH and VL gene pairs were amplified by reverse transcriptasePCR (RT–PCR) using RM21 Ig primers as described previously and produced as recombinant IgG using the strategy outlined in Fig. 3a
We found that AGM Ig heavy and light-chain germline genes are structured and highly homologous with those of RMs and humans, albeit more homologous to RMs than to humans (Fig. 1 and Supplementary Figs 4 and 5)

Summary

Introduction

African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV). We define features of the AGM Ig loci and compare the proportion of Env-specific memory B-cell populations to that of HIV-infected humans and SIV-infected rhesus monkeys. AGMs develop autologous neutralizing responses in plasma and breast milk more rapidly than SIV-infected RMs. AGMs are a potentially unique NHP model for defining induction pathways of antibody responses to SIV/HIV infection and vaccination. The Ig loci of RMs has recently been assembled[11] and a more accurate database of heavy chain variable (VH) germline genes was recently defined[12], making it possible to accurately assess the similarity of vaccineelicited antibody responses in RMs and humans These studies cannot be performed in natural SIV hosts due to the lack of VH germline gene database. Interrogating the nature of this gp120-biased response in natural SIV hosts could assist in the development of vaccination strategies in humans aimed at eliciting functional gp120-specific responses

Methods

Results

Conclusion