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Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses

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Title: Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses
Authors: Tang, X
Guo, J
Cheng, L
Sun, C
Liu, L
Zuo, T
Wang, H
Chen, L
Zhang, L
Chen, Z
Item Type: Journal Article
Abstract: An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain. Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively. Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity. ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer. Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239. Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
Issue Date: 31-Mar-2017
Date of Acceptance: 17-Mar-2017
URI: http://hdl.handle.net/10044/1/48766
DOI: https://dx.doi.org/10.1016/j.vaccine.2017.03.062
ISSN: 0264-410X
Publisher: Elsevier
Start Page: 2582
End Page: 2591
Journal / Book Title: Vaccine
Volume: 35
Issue: 19
Copyright Statement: © 2017 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Virology
06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Notes: publisher: Elsevier articletitle: Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses journaltitle: Vaccine articlelink: http://dx.doi.org/10.1016/j.vaccine.2017.03.062 content_type: article copyright: © 2017 Elsevier Ltd. All rights reserved.
Publication Status: Published
Appears in Collections:Department of Medicine (up to 2019)