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Elicitation of neutralizing antibodies targeting the V2 apex of the HIV envelope trimer in a wild-type animal model

Elicitation of neutralizing antibodies targeting the V2 apex of the HIV envelope trimer in a wild-type animal model
Elicitation of neutralizing antibodies targeting the V2 apex of the HIV envelope trimer in a wild-type animal model

Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response.

Journal Article
2211-1247
222-235
Voss, James E.
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Andrabi, Raiees
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McCoy, Laura E.
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de Val, Natalia
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Fuller, Roberta P.
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Messmer, Terrence
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Su, Ching-Yao
f17d6bf1-d376-40ba-8f14-af7275daeda0
Sok, Devin
036d5259-d0a2-45ea-8436-f4c5a7deafe0
Khan, Salar N.
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Garces, Fernando
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Pritchard, Laura K.
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Wyatt, Richard T.
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Ward, Andrew B.
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Crispin, Max
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Wilson, Ian A.
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Burton, Dennis R.
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Voss, James E.
348679e0-2b5a-4802-8f7b-13f9676197bd
Andrabi, Raiees
b2a7432d-df2b-4d79-bfeb-00d3b02ec65c
McCoy, Laura E.
95af036a-7873-4fdc-b631-e7d7bcbbe98d
de Val, Natalia
17ca4fc8-dfab-41dc-aa68-26de0e9a265c
Fuller, Roberta P.
a351608a-acc9-4e22-9714-c03197aae439
Messmer, Terrence
ad4ed728-eac8-45b1-a230-059838050ceb
Su, Ching-Yao
f17d6bf1-d376-40ba-8f14-af7275daeda0
Sok, Devin
036d5259-d0a2-45ea-8436-f4c5a7deafe0
Khan, Salar N.
0b66dc1d-bc9e-4618-90d5-1f5e1b4b2108
Garces, Fernando
e622015b-b62e-4024-a6ac-7ffce5d3e22f
Pritchard, Laura K.
bfa1d1b4-50b6-401f-b153-8c3322b2e726
Wyatt, Richard T.
39dd4553-50f2-4221-a527-c80d64defc8c
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Wilson, Ian A.
7865d500-d638-4a67-ad6d-fefad0ae83bb
Burton, Dennis R.
a628ce77-b694-4e3c-86a5-11f4e20e1c7c

Voss, James E., Andrabi, Raiees, McCoy, Laura E., de Val, Natalia, Fuller, Roberta P., Messmer, Terrence, Su, Ching-Yao, Sok, Devin, Khan, Salar N., Garces, Fernando, Pritchard, Laura K., Wyatt, Richard T., Ward, Andrew B., Crispin, Max, Wilson, Ian A. and Burton, Dennis R. (2017) Elicitation of neutralizing antibodies targeting the V2 apex of the HIV envelope trimer in a wild-type animal model. Cell Reports, 21 (1), 222-235. (doi:10.1016/j.celrep.2017.09.024).

Record type: Article

Abstract

Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response.

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Accepted/In Press date: 6 September 2017
e-pub ahead of print date: 3 October 2017
Published date: 3 October 2017
Keywords: Journal Article

Identifiers

Local EPrints ID: 418146
URI: http://eprints.soton.ac.uk/id/eprint/418146
ISSN: 2211-1247
PURE UUID: 516556a1-1a7e-4d93-81c4-456931bbeba1
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 22 Feb 2018 17:30
Last modified: 22 Nov 2021 03:16

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Contributors

Author: James E. Voss
Author: Raiees Andrabi
Author: Laura E. McCoy
Author: Natalia de Val
Author: Roberta P. Fuller
Author: Terrence Messmer
Author: Ching-Yao Su
Author: Devin Sok
Author: Salar N. Khan
Author: Fernando Garces
Author: Laura K. Pritchard
Author: Richard T. Wyatt
Author: Andrew B. Ward
Author: Max Crispin ORCID iD
Author: Ian A. Wilson
Author: Dennis R. Burton

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