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Long-term and low-level envelope C2V3 stimulation by highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1-infected individuals

2022-11Contribution to journal Open access
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datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorMartin, Francisco
dc.contributor.authorMarcelino, José Maria
dc.contributor.authorPalladino, Claudia
dc.contributor.authorBártolo, Inês
dc.contributor.authorTracana, Susana
dc.contributor.authorMoranguinho, Inês
dc.contributor.authorGonçalves, Paloma
dc.contributor.authorMateus, Rita
dc.contributor.authorCalado, Rita
dc.contributor.authorBorrego, Pedro
dc.contributor.authorLeitner, Thomas
dc.contributor.authorClemente, Sofia
dc.contributor.authorTaveira, Nuno
dc.date.accessioned2025-11-20T10:32:56Z
dc.date.available2025-11-20T10:32:56Z
dc.date.issued2022-11
dc.description.abstractA minority of HIV-1-infected patients produce broadly neutralizing antibodies (bNAbs). Identification of viral and host correlates of bNAb production may help develop vaccines. We aimed to characterize the neutralizing response and viral and host-associated factors in Angola, which has one of the oldest, most dynamic, and most diverse HIV-1 epidemics in the world. Three hundred twenty-two HIV-1-infected adults from Angola were included in this retrospective study. Phylogenetic analysis of C2V3C3 env gene sequences was used for virus subtyping. Env-binding antibody reactivity was tested against polypeptides comprising the C2, V3, and C3 regions. Neutralizing-antibody responses were determined against a reference panel of tier 2 Env pseudoviruses in TZM-bl cells; neutralizing epitope specificities were predicted using ClustVis. All subtypes were found, along with untypeable strains and recombinant forms. Notably, 56% of the patients developed cross neutralizing, broadly neutralizing, or elite neutralizing responses. Broad and elite neutralization was associated with longer infection time, subtype C, lower CD4+ T cell counts, higher age, and higher titer of C2V3C3-specific antibodies relative to failure to develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients. V3 and C3 regions were significantly less variable in elite neutralizers than in weak neutralizers and nonneutralizers, suggesting an active role of V3C3-directed bNAbs in controlling HIV-1 replication and diversification. In conclusion, prolonged and low-level envelope V3C3 stimulation by highly diverse and ancestral HIV-1 isolates promotes the frequent elicitation of bNAbs. These results provide important clues for the development of an effective HIV-1 vaccine.eng
dc.identifier.citationMartin F, Marcelino JM,Palladino C, Bártolo I, Tracana S, Moranguinho I, Gonçalves P, Mateus R, Calado R, Borrego P, Leitner T, Clemente S, Taveira N, 2022. Long-Term and Low-Level Envelope C2V3 Stimulation by Highly Diverse Virus Isolates Leads to Frequent Development of Broad and Elite Antibody Neutralization in HIV-1-Infected Individuals. Microbiol Spectr 10:e01634-22. https://doi.org/10.1128/spectrum.01634-22
dc.identifier.doi10.1128/spectrum.01634-22
dc.identifier.issn2165-0497
dc.identifier.urihttp://hdl.handle.net/10400.26/59879
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Society for Microbiology
dc.relation.hasversionhttps://doi.org/10.1128/spectrum.01634-22
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAngola
dc.subjectEnv diversity
dc.subjectHIV-1 infection
dc.subjectbroadly neutralizing antibodies
dc.subjectbNAbs
dc.subjectEnv-specific antibodies
dc.subjectneutralizing epitopes
dc.titleLong-term and low-level envelope C2V3 stimulation by highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1-infected individualseng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.issue6
oaire.citation.startPagee01634-22
oaire.citation.titleMicrobiology Spectrum
oaire.citation.volume10
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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