{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:57:37Z","timestamp":1782280657482,"version":"3.54.5"},"posted":{"date-parts":[[2025,10,1]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Broadly neutralizing antibodies targeting multiple sites of HIV-1 Env vulnerability can be induced by infection, but simultaneous elicitation of neutralizing antibodies (NAbs) against multiple epitopes has not yet been achieved by vaccination. In this study, we designed a dual-epitope vaccine targeting both fusion peptide (FP) and V2 apex and evaluated its capacity to induce NAbs against both epitopes in rhesus macaques. This vaccine combined an FP conjugate with a cocktail of engineered Env trimers with enhanced V2 apex recognition and increased antigen retention in lymph nodes. Immunization of macaques with the dual-epitope vaccine elicited &gt;1000-fold higher autologous tier 2-neutralization titers than the wildtype Env trimer and enhanced heterologous NAb breadth. Both FP and V2-apex monoclonal antibodies (mAb) were isolated from immunized macaques and showed heterologous neutralization with genetic and structural signatures that were similar to well-characterized FP and V2 apex bNAbs, although the V2 apex mAbs showed incomplete maturation. These results demonstrate proof-of-concept for simultaneous vaccine elicitation of NAbs against multiple sites of Env vulnerability, which will likely be critical for an effective HIV-1 vaccine.<\/jats:p>\n                <jats:sec>\n                  <jats:title>HIGHLIGHTS<\/jats:title>\n                  <jats:p>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Designed a dual-epitope vaccine targeting both fusion peptide (FP) and V2 apex<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>V2-SET Env trimer conferred higher binding of V2 apex bNAbs, longer retention in draining lymph nodes, and &gt;1000-fold higher induction of autologous neutralization titers compared with wildtype Env trimer<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Dual-epitope vaccine enhanced serum tier 2 neutralization breadth<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Dual-epitope vaccine elicited FP\u2013 and V2 apex-specific neutralizing mAbs with genetic signatures similar to well-characterized FP and V2 apex bNAbs<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.29.679292","type":"posted-content","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T20:55:18Z","timestamp":1759352118000},"source":"Crossref","is-referenced-by-count":0,"title":["Vaccine Elicitation of HIV-1 Neutralizing Antibodies Against Both V2 Apex and Fusion Peptide in Rhesus Macaques"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-9493","authenticated-orcid":false,"given":"Hongying","family":"Duan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-9765","authenticated-orcid":false,"given":"Joseph P.","family":"Nkolola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuishu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayeshbhai","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4704-7100","authenticated-orcid":false,"given":"I-Ting","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Lavine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danealle K.","family":"Parchment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S.","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisha","family":"McKee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijy","family":"O\u2019Dell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misook","family":"Choe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijuan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A. 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