In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 4 ( 2021-4-7), p. e1008977-
Abstract:
Evaluating the structure-function relationship of viral envelope (Env) evolution and the development of broadly cross-neutralizing antibodies (bnAbs) in natural infection can inform rational immunogen design. In the present study, we examined the magnitude and specificity of autologous neutralizing antibodies induced in rabbits by a novel HIV-1 clade C Env protein (1PGE-THIVC) vis-à-vis those developed in an elite neutralizer from whom the env sequence was obtained that was used to prepare the soluble Env protein. The novel 1PGE-THIVC Env trimer displayed a native like pre-fusion closed conformation in solution as determined by small angle X-ray scattering (SAXS) and negative stain electron microscopy (EM). This closed spike conformation of 1PGE-THIVC Env trimers was correlated with weak or undetectable binding of non-neutralizing monoclonal antibodies (mAbs) compared to neutralizing mAbs. Furthermore, 1PGE-THIVC SOSIP induced potent neutralizing antibodies in rabbits to autologous virus variants. The autologous neutralizing antibody specificity induced in rabbits by 1PGE-THIVC was mapped to the C3/V4 region (T362/P401) of viral Env. This observation agreed with electron microscopy polyclonal epitope mapping (EMPEM) of the Env trimer complexed with IgG Fab prepared from the immunized rabbit sera. Our study demonstrated neutralization of sequence matched and unmatched autologous viruses by serum antibodies induced in rabbits by 1PGE-THIVC and also highlighted a comparable specificity for the 1PGE-THIVC SOSIP trimer with that seen with polyclonal antibodies elicited in the elite neutralizer by negative-stain electron microscopy polyclonal epitope (ns-EMPEM) mapping.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1008977
DOI:
10.1371/journal.ppat.1008977.g001
DOI:
10.1371/journal.ppat.1008977.g002
DOI:
10.1371/journal.ppat.1008977.g003
DOI:
10.1371/journal.ppat.1008977.g004
DOI:
10.1371/journal.ppat.1008977.g005
DOI:
10.1371/journal.ppat.1008977.g006
DOI:
10.1371/journal.ppat.1008977.g007
DOI:
10.1371/journal.ppat.1008977.g008
DOI:
10.1371/journal.ppat.1008977.t001
DOI:
10.1371/journal.ppat.1008977.t002
DOI:
10.1371/journal.ppat.1008977.t003
DOI:
10.1371/journal.ppat.1008977.s001
DOI:
10.1371/journal.ppat.1008977.s002
DOI:
10.1371/journal.ppat.1008977.s003
DOI:
10.1371/journal.ppat.1008977.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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