A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Abstract The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomann...

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Autores principales:	Jean-François Bruxelle, Tess Kirilenko, Nino Trattnig, Yiqiu Yang, Matteo Cattin, Paul Kosma, Ralph Pantophlet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6e82ed37f9564815b8027762ff199af6
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spelling	oai:doaj.org-article:6e82ed37f9564815b8027762ff199af62021-12-02T13:30:50ZA glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies10.1038/s41598-021-84116-w2045-2322https://doaj.org/article/6e82ed37f9564815b8027762ff199af62021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84116-whttps://doaj.org/toc/2045-2322Abstract The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.Jean-François BruxelleTess KirilenkoNino TrattnigYiqiu YangMatteo CattinPaul KosmaRalph PantophletNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jean-François Bruxelle Tess Kirilenko Nino Trattnig Yiqiu Yang Matteo Cattin Paul Kosma Ralph Pantophlet A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
description	Abstract The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.
format	article
author	Jean-François Bruxelle Tess Kirilenko Nino Trattnig Yiqiu Yang Matteo Cattin Paul Kosma Ralph Pantophlet
author_facet	Jean-François Bruxelle Tess Kirilenko Nino Trattnig Yiqiu Yang Matteo Cattin Paul Kosma Ralph Pantophlet
author_sort	Jean-François Bruxelle
title	A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
title_short	A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
title_full	A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
title_fullStr	A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
title_full_unstemmed	A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
title_sort	glycoside analog of mammalian oligomannose formulated with a tlr4-stimulating adjuvant elicits hiv-1 cross-reactive antibodies
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6e82ed37f9564815b8027762ff199af6
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A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

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