Immunogenicity and safety following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M<sup>TM</sup> 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
Creators: name: Shinde, Vivek
name: Koen, Anthonet Lombard
name: Hoosain, Zaheer
name: Archary, Moherndran
name: Bhorat, Qasim
name: Fairlie, Lee
name: Lalloo, Umesh
name: Masilela, Mduduzi S. L.
name: Moodley, Dhayendre
name: Hanley, Sherika
name: Fouche, Leon Frederik
name: Louw, Cheryl
name: Tameris, Michele
name: Singh, Nishanta
name: Goga, Ameena
name: Dheda, Keertan
name: Grobbelaar, Coert
name: Joseph, Natasha
name: Lombaard, Johan J.
name: Mngqibisa, Rosie
name: Bhorat, As’ad Ebrahim
name: Benadé, Gabriella
name: Lalloo, Natasha
name: Pitsi, Anna
name: Vollgraaff, Pieter-Louis
name: Luabeya, Angelique
name: Esmail, Aliasgar
name: Petrick, Friedrich G.
name: Jose, Aylin Oommen
name: Foulkes, Sharne
name: Ahmed, Khatija
name: Thombrayil, Asha
name: Kalonji, Dishiki
name: Cloney-Clark, Shane
name: Zhu, Mingzhu
name: Bennett, Chijioke
name: Albert, Gary
name: Marcheschi, Alex
name: Plested, Joyce S.
name: Neal, Susan
name: Chau, Gordon
name: Cho, Iksung
name: Fries, Louis
name: Glenn, Greg M.
name: Madhi, Shabir A.
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Sociology
subject: FOS: Sociology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: COVID-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, MN<sub>50</sub> 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.