{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:27:04Z","timestamp":1791250024449,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["L222069"],"award-info":[{"award-number":["L222069"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Ditan Hospital Outstanding Young Talent Development Program","award":["ZZ202403"],"award-info":[{"award-number":["ZZ202403"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFC2306000"],"award-info":[{"award-number":["2023YFC2306000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection\u2014termed hybrid immunity\u2014typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4\/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4\/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4+ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4\/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity\u2014conferred by vaccination followed by BF.7 or BA.4\/5 breakthrough infection\u2014with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group.<\/jats:p>","DOI":"10.3390\/vaccines14040339","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antibody Responses After BA.5\/BF.7 Breakthrough Infection in People Living with HIV"],"prefix":"10.3390","volume":"14","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Center for HIV\/AIDS, Beijing Ditan Hospital, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaruo","family":"Qiu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglin","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Center for HIV\/AIDS, Beijing Ditan Hospital, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leidan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Center for HIV\/AIDS, Beijing Ditan Hospital, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danying","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1286-5733","authenticated-orcid":false,"given":"Xuesen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Center for HIV\/AIDS, Beijing Ditan Hospital, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nri2524","article-title":"B cells in HIV infection and disease","volume":"9","author":"Moir","year":"2009","journal-title":"Nat. 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