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

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 clinica...

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Main Authors: 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
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Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2425147
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author 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
author_facet 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
author_sort Vivek Shinde
collection DOAJ
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, 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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spelling doaj-art-90d0e4a6be6e439a95268e85ec023ca22025-08-20T03:22:21ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2425147Immunogenicity 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 trialVivek Shinde0Anthonet Lombard Koen1Zaheer Hoosain2Moherndran Archary3Qasim Bhorat4Lee Fairlie5Umesh Lalloo6Mduduzi S. L. Masilela7Dhayendre Moodley8Sherika Hanley9Leon Frederik Fouche10Cheryl Louw11Michele Tameris12Nishanta Singh13Ameena Goga14Keertan Dheda15Coert Grobbelaar16Natasha Joseph17Johan J. Lombaard18Rosie Mngqibisa19As’ad Ebrahim Bhorat20Gabriella Benadé21Natasha Lalloo22Anna Pitsi23Pieter-Louis Vollgraaff24Angelique Luabeya25Aliasgar Esmail26Friedrich G. Petrick27Aylin Oommen Jose28Sharne Foulkes29Khatija Ahmed30Asha Thombrayil31Dishiki Kalonji32Shane Cloney-Clark33Mingzhu Zhu34Chijioke Bennett35Gary Albert36Alex Marcheschi37Joyce S. Plested38Susan Neal39Gordon Chau40Iksung Cho41Louis Fries42Greg M. Glenn43Shabir A. Madhi44Research and Development, Novavax, Inc, Gaithersburg, MD, USASouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaResearch and Development, Josha Research Centre, Bloemfontein, Free State, South AfricaPaediatric Infectious Diseases Unit, University of KwaZulu-Natal, Durban, South AfricaResearch and Development, Soweto Clinical Trials Centre, Johannesburg, South AfricaWits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaRespiratory and Critical Care Unit, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaResearch and Development, Setshaba Research Centre, Tshwane, South AfricaDepartment of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa (CAPRISA), and Department of Family Medicine, University of KwaZulu-Natal, Durban, South AfricaResearch and Development, Limpopo Clinical Research Initiative, Thabazimbi, South AfricaResearch and Development, Madibeng Centre for Research, Brits, South AfricaSouth African TB Vaccine Initiative, University of Cape Town, Cape Town, South AfricaSouth African Medical Research Council, HIV and other Infectious Diseases Research Unit (HIDRU) and, Health Systems Research Unit, Durban, South AfricaSouth African Medical Research Council, HIV and other Infectious Diseases Research Unit (HIDRU) and, Health Systems Research Unit, Durban, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South AfricaAurum Institute, University of Pretoria, Pretoria, South AfricaResearch and Development, PEERMED Clinical Trial Centre, Kempton Park, South AfricaResearch and Development, Josha Research Centre, Bloemfontein, Free State, South AfricaPaediatric Infectious Diseases Unit, University of KwaZulu-Natal, Durban, South AfricaResearch and Development, Soweto Clinical Trials Centre, Johannesburg, South AfricaWits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaRespiratory and Critical Care Unit, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaResearch and Development, Setshaba Research Centre, Tshwane, South AfricaResearch and Development, Limpopo Clinical Research Initiative, Thabazimbi, South AfricaSouth African TB Vaccine Initiative, University of Cape Town, Cape Town, South AfricaCentre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South AfricaResearch and Development, MERC Research, Middelburg, South AfricaSouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaResearch and Development, Josha Research Centre, Bloemfontein, Free State, South AfricaResearch and Development, Setshaba Research Centre, Tshwane, South AfricaSouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaSouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USAResearch and Development, Novavax, Inc, Gaithersburg, MD, USASouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCOVID-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.https://www.tandfonline.com/doi/10.1080/21645515.2024.2425147Novavax, Inc.the Bill & Melinda Gates Foundationand the Coalition for Epidemic Preparedness Innovations
spellingShingle 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
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
Novavax, Inc.
the Bill & Melinda Gates Foundation
and the Coalition for Epidemic Preparedness Innovations
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Novavax, Inc.
the Bill & Melinda Gates Foundation
and the Coalition for Epidemic Preparedness Innovations
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2425147
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