Immunogenicity and safety of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine in people living with and without HIV-1 infection: a randomised, controlled, phase 2A/2B trial.

Journal: The lancet. HIV

Volume: 9

Issue: 5

Year of Publication: 2022

Affiliated Institutions:  Vaccines and Infectious Diseases Analytics Research Unit, South African Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa; African Leadership in Vaccinology Expertise, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: shabir.madhi@wits.ac.za. Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa. Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa. Enhancing Care Foundation, Durban, South Africa. Josha Research Centre, Bloemfontein, South Africa. Respiratory and Critical Care Unit, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. Madibeng Centre for Research, Department of Family Medicine, University of Pretoria, Pretoria, South Africa. Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa. Limpopo Clinical Research Initiative, Thabazimbi, South Africa. Setshaba Research Centre, Tshwane, South Africa. HIV Prevention Research Unit, South African Medical Research Council, Verulam and Isipingo Clinical Research Site, Durban, South Africa. Aurum Institute, University of Pretoria, Pretoria, South Africa. Department of Microbiology, University of Pretoria, Pretoria, South Africa; Setshaba Research Centre, Tshwane, South Africa. Vaccines and Infectious Diseases Analytics Research Unit, South African Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa. Soweto Clinical Trials Centre, Johannesburg, South Africa. MERC Research, Kempton Park, South Africa. Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa; Faculty of Infectious and Tropical Diseases, Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, UK. Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa. Health Systems Research Unit and HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa. MERC Research, Middelburg, South Africa. HIV Prevention Research Unit, South Africa Medical Research Council, Isipingo, South Africa. Novavax, Gaithersburg, MD, USA.

Abstract summary 

There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18-84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. People living with HIV-1 were on stable antiretroviral therapy and had an HIV-1 viral load of less than 1000 copies per mL. Vaccine dosage was 5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant, whereas 0·9% saline was used as placebo injection (volume 0·5 mL each). All study staff and participants remained masked to study group assignment. We previously reported an interim analysis on the efficacy and safety of the NVX-CoV2373 vaccine (coprimary endpoints). In this Article, we present an expanded safety analysis for the full cohort of participants and report on the secondary objective of vaccine immunogenicity in the full cohort of people living with HIV-1 and in HIV-negative individuals overall and stratified by baseline SARS-CoV-2 serostatus. This trial is registered with ClinicalTrials.gov, NCT04533399, and the Pan-African Clinical Trials Registry, PACTR202009726132275.Participants were enrolled between Aug 17 and Nov 25, 2020. The safety analysis set included 4164 HIV-negative participants (2089 in the intervention group and 2075 in the placebo group) and 244 people living with HIV-1 (122 in the intervention group and 122 in the placebo group). 1422 (34·1%) of 4164 HIV-negative people and 83 (34·0%) of 244 people living with HIV-1 were categorised as baseline SARS-CoV-2-positive (ie, anti-spike IgG reactive at enrolment or had a reactive SARS-CoV-2 nucleic acid amplification test by 14 days after the second study vaccination). In the NVX-CoV2373 group, solicited local and systemic adverse events were more common in HIV-negative participants (427 [30·6%] local and 401 [28·7%] systemic) than in people living with HIV-1 (20 [25·3%] local and 20 [25·3%] systemic) among those who were baseline SARS-CoV-2-seronegative (naive). Of the serious adverse events that occurred among HIV-negative people (of whom, two [0·1%] were baseline SARS-CoV-2-negative and four [0·6%] were baseline SARS-CoV-2-positive) and people living with HIV-1 (for whom there were no serious adverse events) in the NVX-CoV2373 group, none were assessed as related to the vaccine. Among participants who were baseline SARS-CoV-2-negative in the NVX-CoV2373 group, the anti-spike IgG geometric mean titres (GMTs) and seroconversion rates (SCRs) were lower in people living with HIV-1 (n=62) than in HIV-negative people (n=1234) following the first vaccination (GMT: 508·6 vs 1195·3 ELISA units [EU]/mL; SCR: 51·6% vs 81·3%); and similarly so 14 days after the second vaccination for GMTs (14 420·5 vs 31 631·8 EU/mL), whereas the SCR was similar at this point (100·0% vs 99·3%). In the NVX-CoV2373 group, anti-spike IgG GMTs 14 days after the second vaccination were substantially higher in those who were baseline SARS-CoV-2-positive than in those who were baseline SARS-CoV-2-seronegative for HIV-negative participants (100 666·1 vs 31 631·8 EU/mL) and for people living with HIV-1 (98 399·5 vs 14 420·5 EU/mL). This was also the case for angiotensin-converting enzyme 2 receptor-binding antibody and neutralising antibody titres.The safety of the NVX-CoV2373 vaccine in people living with HIV-1 was similar to that in HIV-negative participants. However, people living with HIV-1 not previously exposed to SARS-CoV-2 had attenuated humoral immune responses to NVX-CoV2373 compared with their HIV-negative vaccine counterparts, but not so if they were baseline SARS-CoV-2-positive.Novavax and the Bill & Melinda Gates Foundation; investigational vaccine manufacturing support was provided by the Coalition for Epidemic Preparedness Innovations.

Authors & Co-authors:  Madhi Shabir A SA Moodley Dhayendre D Hanley Sherika S Archary Moherndran M Hoosain Zaheer Z Lalloo Umesh U Louw Cheryl C Fairlie Lee L Fouche Leon Frederik LF Masilela Mduduzi S L MSL Singh Nishanta N Grobbelaar Coert C Ahmed Khatija K Benadé Gabriella G Bhikha Sutika S Bhorat As'ad Ebrahim AE Bhorat Qasim Q Joseph Natasha N Dheda Keertan K Esmail Aliasgar A Foulkes Sharne S Goga Ameena A Oommen Jose Aylin A Kruger Gertruida G Kalonji Dishiki J DJ Lalloo Natasha N Lombaard Johan J JJ Lombard Koen Anthonet A Kany Luabeya Angelique A Mngqibisa Rosie R Petrick Friedrich G FG Pitsi Annah A Tameris Michele M Thombrayil Asha A Vollgraaff Pieter-Louis PL Cloney-Clark Shane S Zhu Mingzhu M Bennett Chijioke C Albert Gary G Faust Emmanuel E Plested Joyce S JS Fries Lou L Robertson Andreana A Neal Susan S Cho Iksung I Glenn Greg M GM Shinde Vivek V

Study Outcome 

Source Link: Visit source

Statistics
Citations :  UNAIDS Fact sheet—World Aids Day 2021. Nov 29, 2021. https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf
Authors :  48
Identifiers
Doi : 10.1016/S2352-3018(22)00041-8
SSN : 2352-3018
Study Population
Male,Female
Mesh Terms
Adjuvants, Immunologic
Other Terms
Study Design
Cohort Study,Case Study,Cross Sectional Study
Study Approach
Systemic Review
Country of Study
South Africa
Publication Country
Netherlands