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dc.contributor.authorBeltran-Pavez, Carolina
dc.contributor.authorBontjer, Ilja
dc.contributor.authorGonzalez-Fernandez, Nuria 
dc.contributor.authorPernas, Maria 
dc.contributor.authorMerino-Mansilla, Alberto 
dc.contributor.authorOlvera, Alex
dc.contributor.authorMiro, Jose M
dc.contributor.authorBrander, Christian
dc.contributor.authorAlcamí, José 
dc.contributor.authorSanders, Rogier W
dc.contributor.authorSanchez-Merino, Victor 
dc.contributor.authorYuste-Herranz, Maria Eloisa
dc.identifier.citationJ Virol. 2022 Jan 12;96(1):e0134321.es_ES
dc.description.abstractLongitudinal studies in HIV-1 infected individuals have indicated that 2-3 years of infection are required to develop broadly neutralizing antibodies. However, we have previously identified individuals with broadly neutralizing activity (bNA) in early HIV-1 infection, indicating that a vaccine may be capable of bNA induction after short periods of antigen exposure. Here, we describe 5 HIV-1 envelope sequences from individuals who have developed bNA within the first 100 days of infection (early neutralizers) and selected two of them to design immunogens based on HIV-1-Gag virus like particles (VLPs). These VLPs were homogeneous and incorporated the corresponding envelopes (7 to 9μg of gp120 in 1010 VLPs). Both envelopes bound to well-characterized bNAbs, including trimer-specific antibodies (PGT145, VRC01 and 35022). For immunogenicity testing, we immunized rabbits with the Env-VLPs or with the corresponding stabilized soluble Envelope trimers. A short immunization protocol (105 days) was used to recapitulate the early nAb induction observed after HIV-1 infection in these two individuals. All VLP and trimeric Envelope immunogens induced a comparably strong anti-gp120 response, despite having immunized rabbits with 30 times less gp120 in the case of the Env-VLPs. In addition, animals immunized with VLP-formulated Envs induced antibodies that cross-recognized the corresponding soluble stabilized trimer and vice versa, even though no neutralizing activity was observed. Nevertheless, our data may provide a new platform of immunogens, based on HIV-1 envelopes from patients with early broadly neutralizing responses, with the potential to generate protective immune responses using vaccination protocols similar to those used in classical preventive vaccines. Importance: It is generally accepted that an effective HIV-1 vaccine should be able to induce broad-spectrum neutralizing antibodies. Since most of these antibodies require long periods of somatic maturation in vivo, several groups are developing immunogens, based on the HIV envelope protein, that require complex and lengthy immunization protocols that would be difficult to implement to the general population. Here, we show that rabbits immunized with new envelopes (VLP-formulated) from two individuals who demonstrated broadly neutralizing activity very early after infection, induced specific HIV-1 antibodies after a short immunization protocol. This evidence provides the basis for generating protective immune responses with classic vaccination protocols with vaccine prototypes based on HIV envelope sequences from individuals who have developed early broadly neutralizing responses.es_ES
dc.description.sponsorshipThis project received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 681137 to I.B., N.G., A.O., C.B., J.A., R.W.S., and E.Y. It was also partially supported by the Spanish AIDS Research Network (RIS), funded by the Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF) “A way to build Europe” (projects RD16CIII/0002/0001, RD16CIII/0002/0005, and RD16CIII/0025/0041), Plan Estatal de I1D1I 2013-2016 to N.G., A.M.M., J.A., V.S.M., E.Y., M.P., A.O., and C.B.; by IDIBAPS to J.M.M. (80:20 Research grant); by the Fondation Dormeur, Vaduz to C.B.; by the Ministerio de Economía, Industria y Competitividad to N.G., V.S.M., and E.Y. (PI17CIII/00049); by the Ministerio de Ciencia e Innovación to N.G., V.S.M., and E.Y. (PI20CIII/00039); by the Consejo Nacional de Innovación, Ciencia y Tecnología to C.B.P.; and by the HHS/ National Institutes of Health (NIH) to C.B. (P01-AI131568).es_ES
dc.publisherAmerican Society for Microbiology (ASM) es_ES
dc.subjectNeutralizing antibodieses_ES
dc.subjectVirus-like particleses_ES
dc.titlePotent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responseses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderUnión Europea. Comisión Europea. H2020 es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderRed de Investigación Cooperativa en Investigación en Sida (España) es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.contributor.funderPlan Nacional de I+D+i (España) es_ES
dc.contributor.funderFondation Martin Bodmeres_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) es_ES
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España) es_ES
dc.contributor.funderUnited States Department of Health and Human Services es_ES
dc.identifier.journalJournal of virologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.rights.accessRightsopen accesses_ES

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