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An HIV-1/HIV-2 Chimeric Envelope Glycoprotein Generates Binding and Neutralising Antibodies against HIV-1 and HIV-2 Isolates

2023-05-22Artigo científico Acesso aberto
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dc.contributor.authorTaveira, Nuno
dc.contributor.authorFigueiredo, Inês
dc.contributor.authorCalado, Rita
dc.contributor.authorMartin, Francisco
dc.contributor.authorBártolo, Inês
dc.contributor.authorMarcelino, José Maria
dc.contributor.authorBorrego, Pedro
dc.contributor.authorCardoso, Fernando M H
dc.contributor.authorBarroso, Helena
dc.date.accessioned2024-01-18T18:25:32Z
dc.date.available2024-01-18T18:25:32Z
dc.date.issued2023-05-22
dc.date.updated2023-10-25T13:01:58Z
dc.description© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractThe development of immunogens that elicit broadly reactive neutralising antibodies (bNAbs) is the highest priority for an HIV vaccine. We have shown that a prime-boost vaccination strategy with vaccinia virus expressing the envelope glycoprotein gp120 of HIV-2 and a polypeptide comprising the envelope regions C2, V3 and C3 elicits bNAbs against HIV-2. We hypothesised that a chimeric envelope gp120 containing the C2, V3 and C3 regions of HIV-2 and the remaining parts of HIV-1 would elicit a neutralising response against HIV-1 and HIV-2. This chimeric envelope was synthesised and expressed in vaccinia virus. Balb/c mice primed with the recombinant vaccinia virus and boosted with an HIV-2 C2V3C3 polypeptide or monomeric gp120 from a CRF01_AG HIV-1 isolate produced antibodies that neutralised >60% (serum dilution 1:40) of a primary HIV-2 isolate. Four out of nine mice also produced antibodies that neutralised at least one HIV-1 isolate. Neutralising epitope specificity was assessed using a panel of HIV-1 TRO.11 pseudoviruses with key neutralising epitopes disrupted by alanine substitution (N160A in V2; N278A in the CD4 binding site region; N332A in the high mannose patch). The neutralisation of the mutant pseudoviruses was reduced or abolished in one mouse, suggesting that neutralising antibodies target the three major neutralising epitopes in the HIV-1 envelope gp120. These results provide proof of concept for chimeric HIV-1/HIV-2 envelope glycoproteins as vaccine immunogens that can direct the antibody response against neutralising epitopes in the HIV-1 and HIV-2 surface glycoproteins.pt_PT
dc.description.sponsorshipThis work was funded by national funds through the FCT-Foundation for Science and Technology, I.P., under the project UIDB/04585/2020, by FCT and Aga Khan Development Network (AKDN)—Portugal Collaborative Research Network in Portuguese speaking countries in Africa, project 332821690 and by Ministry of Health, Portugal, project HIV/SAU/0008.11.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationTaveira N, Figueiredo I, Calado R, Martin F, Bártolo I, Marcelino JM, et al. An hiv-1/hiv-2 chimeric envelope glycoprotein generates binding and neutralising antibodies against hiv-1 and hiv-2 isolates. IJMS [Internet]. 22 de maio de 2023;24(10):9077. Disponível em: https://www.mdpi.com/1422-0067/24/10/9077pt_PT
dc.identifier.doi10.3390/ijms24109077pt_PT
dc.identifier.slugcv-prod-3359446
dc.identifier.urihttp://hdl.handle.net/10451/61921
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationEgas Moniz Interdisciplinary Research Center
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/24/10/9077pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHIV vaccinept_PT
dc.subjectchimeric envelope glycoproteinspt_PT
dc.subjectvaccinia viruspt_PT
dc.subjectneutralizing antibodiespt_PT
dc.subjectneutralizing epitopespt_PT
dc.titleAn HIV-1/HIV-2 Chimeric Envelope Glycoprotein Generates Binding and Neutralising Antibodies against HIV-1 and HIV-2 Isolatespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberUIDB/04585/2020
oaire.awardTitleEgas Moniz Interdisciplinary Research Center
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04585%2F2020/PT
oaire.citation.issue10pt_PT
oaire.citation.startPage9077pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume24pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameTaveira
person.familyNameMartin
person.familyNameBártolo
person.familyNameMARCELINO
person.familyNameBorrego
person.familyNameCardoso
person.familyNameBarroso
person.givenNameNuno
person.givenNameFrancisco
person.givenNameInês
person.givenNameJOSÉ MARIA
person.givenNamePedro
person.givenNameFernando
person.givenNameHelena
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person.identifier.orcid0000-0003-0176-5585
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person.identifier.scopus-author-id12240839300
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.cv.cienciaid661E-F5CB-F85A | Inês Bártolo
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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