Development of broad neutralization activity in simian/human immunodeficiency virus-infected rhesus macaques after long-term infection.

Journal Article

Nonhuman primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 envelope 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.Neutralization breadth and specificities in plasmas from SHIV-infected macaques were determined by analyzing a panel of tier 2 viruses and their mutants.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 envelope-pseudoviruses.Longitudinal plasma from three SHIVSF162P3-infected macaques and three SHIV1157ipd3N4-infected macaques rarely neutralized viruses (<25%) within 1 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, whereas none of macaques infected with SHIVSF162P3 or SHIVCHN19P4 could neutralize more than 25% of viruses after 6 years of infection (Pā€Š=ā€Š0.035). 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.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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • March 2018

Published In

Volume / Issue

  • 32 / 5

Start / End Page

  • 555 - 563

PubMed ID

  • 29239895

Electronic International Standard Serial Number (EISSN)

  • 1473-5571

International Standard Serial Number (ISSN)

  • 0269-9370

Digital Object Identifier (DOI)

  • 10.1097/qad.0000000000001724

Language

  • eng