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

被引：13

作者：

Gao, Nan ^{[1
]}

Wang, Wei ^{[2
,3
]}

Wang, Chu ^{[1
]}

Gu, Tiejun ^{[1
,4
]}

Guo, Rui ^{[1
]}

Yu, Bin ^{[1
,4
]}

Kong, Wei ^{[1
,4
]}

Qin, Chuan ^{[2
,3
]}

Giorgi, Elena E. ^{[5
]}

Chen, Zhiwei ^{[6
,7
]}

Townsley, Samantha ^{[8
]}

Hu, Shiu-Lok ^{[8
]}

Yu, Xianghui ^{[1
,4
]}

Gao, Feng ^{[1
,9
]}

机构：

[1] Jilin Univ, Sch Life Sci, Natl Engn Lab AIDS Vaccine, Changchun, Jilin, Peoples R China

[2] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China

[3] Peking Union Med Coll, Comparat Med Ctr, Beijing, Peoples R China

[4] Jilin Univ, Sch Life Sci, Minist Educ, Key Lab Mol Enzymol & Engn, Changchun, Jilin, Peoples R China

[5] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA

[6] Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Infect & Immun, AIDS Inst, Pok Fu Lam, Hong Kong, Peoples R China

[7] Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Infect & Immun, Dept Microbiol, Pok Fu Lam, Hong Kong, Peoples R China

[8] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA

[9] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

来源：

AIDS | 2018年 / 32卷 / 05期

基金：

中国国家自然科学基金;

关键词：

infection; macaques; maturation; neutralization; simian; human immunodeficiency virus; ANTIBODY-RESPONSES; GP120; SHIV-1157IPD3N4; INDUCTION; ENVELOPE; CHINESE; CELLS; PANEL; AIDS;

D O I：

10.1097/QAD.0000000000001724

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objective: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.Design:Neutralization breadth and specificities in plasmas from SHIV-infected macaques were 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 envelope-pseudoviruses.Results: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 (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.Conclusion: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.

引用

页码：555 / 563

页数：9