Safety, Effectiveness and Immunogenicity of heterologous mRNA-1273 Boost

South Africa

Nigel Garrett, Tarylee Reddy, Nonhlanhla Yende-Zuma, Azwidhwi Takalani, Kubashni Woeber, Annie Bodenstein, Phumeza Jonas, Imke Engelbrecht, Waasila Jassat, Harry Moultrie, Debbie Bradshaw, Ishen Seocharan, Jackline Odhiambo, Kentse Khuto, Simone I. Richardson, Millicent A. Omondi, Rofhiwa Nesamari,

Identification

Survey ID Number

SafetyEffectivenessandImmunogenicityofheterologousmRNA-1273Boost

Title

Safety, Effectiveness and Immunogenicity of heterologous mRNA-1273 Boost

Country

Name	Country code
South Africa	ZAR

Abstract

Given limited data on safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income, high-HIV prevalence settings, we evaluated a mRNA-1273 boost after Ad26.COV2.S priming in South Africa. SHERPA was a single-arm, open-label, phase 3 study nested in the Sisonke implementation trial of 500000 healthcare workers (HCWs). Sisonke participants were offered mRNA-1273 boosters between May and November 2022, a period of circulating Omicron sub-lineages. Adverse events (AE) were self-reported, and co-primary endpoints (SARS-CoV-2 infections and COVID-19 hospitalizations or deaths) were collected through national databases. We used Cox regression models with booster status as time-varying covariate to determine the relative vaccine effectiveness (rVE) of the mRNA-1273 booster among SHERPA versus unboosted Sisonke participants. Of 11248 SHERPA participants in the rVE analysis cohort (79.3% female, median age 41), 45.4% had received one and 54.6% two Ad26.COV2.S doses. Self-reported comorbidities included HIV (18.7%), hypertension (12.9%) and diabetes (4.6%). In multivariable analysis including 413161 unboosted Sisonke participants, rVE of the booster was 59% (95%CI 29-76%) against SARS-CoV-2 infection: 77% (95%CI 9-94%) in the one-Ad26.COV2.S dose group and 52% (95%CI 13-73%) in the two-dose group. Severe COVID-19 was identified in 148 unboosted participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 271 (2.3%) reported a reactogenicity event or unsolicited AE, more among those with prior SARS-CoV-2 infections (adjusted odds ratio [aOR] 2.03, 95%CI 1.59-2.59) and less among people living with HIV (PLWH) (aOR 0.49, 95%CI 0.34-0.69). No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased antibody functions and T-cell responses 4 weeks after boosting regardless of the number of prior Ad26.COV2.S doses, or HIV status, and generated Omicron spike-specific crossreactive responses. mRNA-1273 boosters after one or two Ad26.COV2.S doses were well-tolerated, safe and effective against Omicron SARS-CoV-2 infections among HCWs and PLWH.

Producers and sponsors

Primary investigators

Name	Affiliation
Nigel Garrett	Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
Tarylee Reddy	Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa
Nonhlanhla Yende-Zuma	Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa
Azwidhwi Takalani	Hutchinson Center Research Institute of South Africa, Cape Town, South Africa
Kubashni Woeber	Grants, Innovation and Product Development Unit, SAMRC, Durban, South Africa
Annie Bodenstein	Right to Care, Johannesburg, Gauteng, South Africa
Phumeza Jonas	Right to Care, Johannesburg, Gauteng, South Africa
Imke Engelbrecht	Right to Care, Johannesburg, Gauteng, South Africa
Waasila Jassat	Division of Public Health Surveillance and Response, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Services (NHLS), Johannesburg, South Africa
Harry Moultrie	Division of Public Health Surveillance and Response, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Services (NHLS), Johannesburg, South Africa
Debbie Bradshaw	Burden of Disease Research Unit, SAMRC, Tygerberg, South Africa
Ishen Seocharan	Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa
Jackline Odhiambo	Hutchinson Center Research Institute of South Africa, Cape Town, South Africa
Kentse Khuto	Hutchinson Center Research Institute of South Africa, Cape Town, South Africa
Simone I. Richardson	SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Millicent A. Omondi	Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Rofhiwa Nesamari	Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Roanne S. Keeton	Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Catherine Riou	Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa
Thandeka Moyo-Gwete	SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Penny L. Moore	SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa.
Wendy A. Burgers	Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Kate Anteyi	Moderna Inc., Cambridge, MA, USA
Brett Leav	Moderna Inc., Cambridge, MA, USA
Linda-Gail Bekker	Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa
Glenda E Gray	Office of the President and CEO, SAMRC, Cape Town, South Africa
Ameena Goga	HIV and other Infectious Diseases Research Unit, SAMRC, Durban, South Africa
SHERPA study team