Shinde, VivekKoen, Anthonet LombardHoosain, ZaheerArchary, MoherndranBhorat, QasimFairlie, LeeLalloo, UmeshMasilela, Mduduzi S.L.Moodley, DhayendreHanley, SherikaFouche, Leon FrederikLouw, CherylTameris, MicheleSingh, NishantaGoga, AmeenaDheda, KeertanGrobbelaar, CoertJoseph, NatashaLombaard , Johan J.Mngqibisa, RosieBhorat, As’ad EbrahimBenade, GabriellaLalloo, NatashaPitsi, AnnaVollgraaff, Pieter-LouisLuabeya, AngeliqueEsmail, AliasgarPetrick, Friedrich G.Jose, Aylin OommenFoulkes, SharneAhmed, KhatijaThombrayil, AshaKalonji, DishikiCloney-Clark, ShaneZhu, MingzhuBennett, ChijiokeAlbert, GaryMarcheschi, AlexPlested, Joyce S.Neal, SusanChau, GordonCho, IksungFries, LouisGlenna, Greg M.Madhi, Shabir A.2025-07-152025-07-152024-12Shinde, V., Loen, A.L., Hoosain, Z. et al. 2024, 'Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-MTM adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa : a randomized crossover phase 2a/2b trial', Human vaccines & immunotherapeutics, vol. 20, no. 1, pp. 1-12. https://doi.org/10.1080/21645515.2024.2425147.2164-5515 (print)2164-554X (online)10.1080/21645515.2024.2425147http://hdl.handle.net/2263/103378COVID-19 remains a global public health issue and an improved understanding of vaccine performance in immunocompromised individuals, including people living with HIV (PLWH), is needed. Initial data from the present study's pre-crossover/booster phase were previously reported. This phase 2a/b clinical trial in South Africa (2019nCoV-501/NCT04533399) revisits 1:1 randomly assigned HIV-negative adults (18-84 years) and medically stable PLWH (18-64 years) who previously received two NVX-CoV2373 doses (5 μg recombinant Spike protein with 50 μg Matrix-M™ adjuvant) or placebo. During the 6-month blinded crossover/booster phase, NVX-CoV2373 recipients could receive a single NVX-CoV2373 booster dose and placebo recipients a 2-dose NVX-CoV2373 primary series. NVX-CoV2373 safety and immunogenicity were assessed according to prior SARS-CoV-2 infection and HIV status. Post-crossover, 1900/3793 NVX-CoV2373 recipients were assigned another dose, and 1893/3793 placebo recipients were assigned NVX-CoV2373 primary series. Approximately 56% of the participants were SARS-CoV-2-seropositive ("seropositive") at crossover (6% PLWH). In seropositive participants (HIV-negative and PLWH), booster-dose anti-spike IgG, MN50 and hACE2 inhibition responses increased to similar levels, exceeding those in seronegative participants. In primary-series and booster cohorts, seronegative PLWH showed higher neutralizing responses (4.9- to 5.5-fold, respectively) versus peak pre-crossover primary-series responses. The safety profile was similar among the pre-crossover/booster phase groups; solicited and unsolicited adverse events were infrequent in all groups. A single NVX-CoV2373 booster dose substantially increased antibodies. All baseline seropositive participants showed higher immune responses than seronegative participants. These findings support use of NVX-CoV2373, including in immunocompromised individuals.en© 2024 Novavax, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License.COVID-19 pandemicPeople living with HIV (PLHIV)Coronavirus disease 2019 (COVID-19)Human immunodeficiency virus (HIV)ImmunogenicitySafetySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-MTM adjuvant (NVX-CoV2373) versus a primary series in people living with and without HIV-1 infection in South Africa : a randomized crossover phase 2a/2b trialArticle