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Development of broad neutralization activity in SHIV-infected rhesus macaques after long-term infection.

Development of broad neutralization activity in SHIV-infected rhesus macaques after long-term infection.
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Gao N, Wang W, Wang C, Gu T, Guo R, Yu B, Kong W, Qin C, Giorgi EE, Chen Z, Townsley S, Hu SL, Yu X, Gao F,


Gao N, Wang W, Wang C, Gu T, Guo R, Yu B, Kong W, Qin C, Giorgi EE, Chen Z, Townsley S, Hu SL, Yu X, Gao F, (click to view)

Gao N, Wang W, Wang C, Gu T, Guo R, Yu B, Kong W, Qin C, Giorgi EE, Chen Z, Townsley S, Hu SL, Yu X, Gao F,

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AIDS (London, England) 2017 12 12() doi 10.1097/QAD.0000000000001724

Abstract
OBJECTIVE
Non-human primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 Env vaccines. However, whether broadly neutralizing antibodies (bnAbs) can be elicited in NHPs infected with simian/human immunodeficiency virus (SHIV) has not been fully understood. The objective of this study is to investigate whether broad neutralization activities were developed in SHIV-infected macaques after long-term infection as in humans.

DESIGN
Neutralization breadth and specificities in plasmas from SHIV-infected macaques could be determined by analyzing a panel of tier 2 viruses and their mutants.

METHODS
Forty-four Chinese macaques infected with SHIV1157ipd3N4, SHIVSF162P3 or SHIVCHN19P4 were followed for 54-321 weeks. Archived plasmas from 19 macaques were used to determine neutralization breadth and specificities against 17 tier 2 Env-pseudoviruses.

RESULTS
Longitudinal plasma from three SHIVSF162P3-infected macaques and three SHIV1157ipd3N4-infected macaques rarely neutralized viruses (<25%) within one year of infection. The neutralization breadth in two SHIV1157ipd3N4-infected macaques significantly increased (≥65%) by year 6. Four of six SHIV1157ipd3N4-infected macaques could neutralize 50%-75% viruses while none of macaques infected with SHIVSF162P3 or SHIVCHN19P4 could neutralize more than 25% of viruses after 6 years of infection (p = 0.035). Neutralization specificity analysis showed mutations resistant to bnAbs in V2, V3 or CD4bs regions could abrogate neutralization by year-6 plasma from three SHIV1157ipd3N4-infected macaques. CONCLUSIONS
These results demonstrate that bnAbs targeting common HIV-1 epitopes can be elicited in SHIV1157ipd3N4-infected macaques as in humans after 4-6 years of infection and SHIV/NHP can serve as an ideal model to study bnAb maturation.

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