{"doc_desc":{"title":"Safety, Effectiveness and Immunogenicity of heterologous mRNA-1273 Boost"},"study_desc":{"title_statement":{"idno":"SafetyEffectivenessandImmunogenicityofheterologousmRNA-1273Boost","title":"Safety, Effectiveness and Immunogenicity of heterologous mRNA-1273 Boost"},"authoring_entity":[{"name":"Nigel Garrett","affiliation":"Centre for the AIDS Programme of Research in South Africa, Durban, South Africa"},{"name":"Tarylee Reddy","affiliation":"Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa"},{"name":"Nonhlanhla Yende-Zuma","affiliation":"Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa"},{"name":"Azwidhwi Takalani","affiliation":"Hutchinson Center Research Institute of South Africa, Cape Town, South Africa"},{"name":"Kubashni Woeber","affiliation":"Grants, Innovation and Product Development Unit, SAMRC, Durban, South Africa"},{"name":"Annie Bodenstein","affiliation":"Right to Care, Johannesburg, Gauteng, South Africa"},{"name":"Phumeza Jonas","affiliation":"Right to Care, Johannesburg, Gauteng, South Africa"},{"name":"Imke Engelbrecht","affiliation":"Right to Care, Johannesburg, Gauteng, South Africa"},{"name":"Waasila Jassat","affiliation":"Division of Public Health Surveillance and Response, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Services (NHLS), Johannesburg, South Africa"},{"name":"Harry Moultrie","affiliation":"Division of Public Health Surveillance and Response, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Services (NHLS), Johannesburg, South Africa"},{"name":"Debbie Bradshaw","affiliation":"Burden of Disease Research Unit, SAMRC, Tygerberg, South Africa"},{"name":"Ishen Seocharan","affiliation":"Biostatistics Research Unit, South African Medical Research Council (SAMRC), Durban, South Africa"},{"name":"Jackline Odhiambo","affiliation":"Hutchinson Center Research Institute of South Africa, Cape Town, South Africa"},{"name":"Kentse Khuto","affiliation":"Hutchinson Center Research Institute of South Africa, Cape Town, South Africa"},{"name":"Simone I. Richardson","affiliation":"SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa."},{"name":"Millicent A. Omondi","affiliation":"Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa"},{"name":"Rofhiwa Nesamari","affiliation":"Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa"},{"name":"Roanne S. Keeton","affiliation":"Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa"},{"name":"Catherine Riou","affiliation":"Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa"},{"name":"Thandeka Moyo-Gwete","affiliation":"SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa."},{"name":"Penny L. Moore","affiliation":"SAMRC Antibody Immunity Research Unit, School of 28 Pathology, University of the Witwatersrand, Johannesburg, South Africa."},{"name":"Wendy A. Burgers","affiliation":"Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa"},{"name":"Kate Anteyi","affiliation":"Moderna Inc., Cambridge, MA, USA"},{"name":"Brett Leav","affiliation":"Moderna Inc., Cambridge, MA, USA"},{"name":"Linda-Gail Bekker","affiliation":"Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa"},{"name":"Glenda E Gray","affiliation":"Office of the President and CEO, SAMRC, Cape Town, South Africa"},{"name":"Ameena Goga","affiliation":"HIV and other Infectious Diseases Research Unit, SAMRC, Durban, South Africa"},{"name":"SHERPA study team","affiliation":""}],"study_info":{"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.","nation":[{"name":"South Africa","abbreviation":"ZAR"}]}}}