RV144 HIV-1 vaccination impacts post-infection antibody responses

Author:

Mdluli ThembiORCID,Jian NingboORCID,Slike BonnieORCID,Paquin-Proulx DominicORCID,Donofrio Gina,Alrubayyi Aljawharah,Gift Syna,Grande RebeccaORCID,Bryson Mary,Lee Anna,Dussupt VincentORCID,Mendez-Riveria Letzibeth,Sanders-Buell EricORCID,Chenine Agnès-Laurence,Tran UrsulaORCID,Li YifanORCID,Brown EricORCID,Edlefsen Paul T.ORCID,O’Connell RobertORCID,Gilbert PeterORCID,Nitayaphan Sorachai,Pitisuttihum Punnee,Rerks-Ngarm Supachai,Robb Merlin L.ORCID,Gramzinski RobertORCID,Alter Galit,Tovanabutra SodsaiORCID,Georgiev Ivelin S.,Ackerman Margaret E.,Polonis Victoria R.,Vasan SandhyaORCID,Michael Nelson L.,Kim Jerome H.ORCID,Eller Michael A.ORCID,Krebs Shelly J.ORCID,Rolland MorganeORCID

Abstract

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

Publisher

Public Library of Science (PLoS)

Subject

Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology

Reference47 articles.

1. Effectiveness of UNAIDS targets and HIV vaccination across 127 countries;J Medlock;Proc Natl Acad Sci U S A,2017

2. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand;S Rerks-Ngarm;N Engl J Med,2009

3. Immune-correlates analysis of an HIV-1 vaccine efficacy trial;BF Haynes;N Engl J Med,2012

4. Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection;S Zolla-Pazner;PLoS One,2014

5. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2;M Rolland;Nature,2012

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3