Human Vaccines & Immunotherapeutics (Dec 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

  • Vivek Shinde,
  • Anthonet Lombard Koen,
  • Zaheer Hoosain,
  • Moherndran Archary,
  • Qasim Bhorat,
  • Lee Fairlie,
  • Umesh Lalloo,
  • Mduduzi S. L. Masilela,
  • Dhayendre Moodley,
  • Sherika Hanley,
  • Leon Frederik Fouche,
  • Cheryl Louw,
  • Michele Tameris,
  • Nishanta Singh,
  • Ameena Goga,
  • Keertan Dheda,
  • Coert Grobbelaar,
  • Natasha Joseph,
  • Johan J. Lombaard,
  • Rosie Mngqibisa,
  • As’ad Ebrahim Bhorat,
  • Gabriella Benadé,
  • Natasha Lalloo,
  • Anna Pitsi,
  • Pieter-Louis Vollgraaff,
  • Angelique Luabeya,
  • Aliasgar Esmail,
  • Friedrich G. Petrick,
  • Aylin Oommen Jose,
  • Sharne Foulkes,
  • Khatija Ahmed,
  • Asha Thombrayil,
  • Dishiki Kalonji,
  • Shane Cloney-Clark,
  • Mingzhu Zhu,
  • Chijioke Bennett,
  • Gary Albert,
  • Alex Marcheschi,
  • Joyce S. Plested,
  • Susan Neal,
  • Gordon Chau,
  • Iksung Cho,
  • Louis Fries,
  • Greg M. Glenn,
  • Shabir A. Madhi

DOI
https://doi.org/10.1080/21645515.2024.2425147
Journal volume & issue
Vol. 20, no. 1

Abstract

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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, 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.

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