TY - JOUR
T1 - Safety, effectiveness and immunogenicity of heterologous mRNA-1273 boost after prime with Ad26.COV2.S among healthcare workers in South Africa
T2 - The single-arm, open-label, phase 3 SHERPA study
AU - the SHERPA study team
AU - Garrett, Nigel
AU - Reddy, Tarylee
AU - Yende-Zuma, Nonhlanhla
AU - Takalani, Azwidhwi
AU - Woeber, Kubashni
AU - Bodenstein, Annie
AU - Jonas, Phumeza
AU - Engelbrecht, Imke
AU - Jassat, Waasila
AU - Moultrie, Harry
AU - Bradshaw, Debbie
AU - Seocharan, Ishen
AU - Odhiambo, Jackline
AU - Khuto, Kentse
AU - Richardson, Simone I.
AU - Omondi, Millicent A.
AU - Nesamari, Rofhiwa
AU - Keeton, Roanne S.
AU - Riou, Catherine
AU - Moyo-Gwete, Thandeka
AU - Innes, Craig
AU - Zwane, Zwelethu
AU - Mngadi, Kathy
AU - Brumskine, William
AU - Naicker, Nivashnee
AU - Potloane, Disebo
AU - Badal-Faesen, Sharlaa
AU - Innes, Steve
AU - Barnabas, Shaun
AU - Lombaard, Johan
AU - Gill, Katherine
AU - Nchabeleng, Maphoshane
AU - Snyman, Elizma
AU - Petrick, Friedrich
AU - Spooner, Elizabeth
AU - Naidoo, Logashvari
AU - Kalonji, Dishiki
AU - Naicker, Vimla
AU - Singh, Nishanta
AU - Maboa, Rebone
AU - Mda, Pamela
AU - Malan, Daniel
AU - Nana, Anusha
AU - Malahleha, Mookho
AU - Kotze, Philip
AU - Allagappen, Jon J.
AU - Diacon, Andreas H.
AU - Kruger, Gertruida M.
AU - Patel, Faeezah
AU - Moore, Penny L.
N1 - Publisher Copyright:
Copyright: © 2024 Garrett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024/12/5
Y1 - 2024/12/5
N2 - Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.S (SHERPA) trial 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, when Omicron sub-lineages were circulating. 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 a 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 Sisonke participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 228 (1.9%) participants reported 575 reactogenicity events within 7 days of the booster (most commonly injection site pain, malaise, myalgia, swelling, induration and fever). More reactogenicity events were reported 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). There were 115 unsolicited adverse events (AEs) within 28 days of vaccination. No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased binding and neutralizing antibody titres and spike-specific 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 cross-reactive 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.
AB - Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.S (SHERPA) trial 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, when Omicron sub-lineages were circulating. 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 a 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 Sisonke participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 228 (1.9%) participants reported 575 reactogenicity events within 7 days of the booster (most commonly injection site pain, malaise, myalgia, swelling, induration and fever). More reactogenicity events were reported 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). There were 115 unsolicited adverse events (AEs) within 28 days of vaccination. No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased binding and neutralizing antibody titres and spike-specific 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 cross-reactive 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.
UR - http://www.scopus.com/inward/record.url?scp=85211576847&partnerID=8YFLogxK
U2 - 10.1371/journal.pgph.0003260
DO - 10.1371/journal.pgph.0003260
M3 - Article
C2 - 39636838
AN - SCOPUS:85211576847
SN - 2767-3375
VL - 4
JO - PLOS Global Public Health
JF - PLOS Global Public Health
IS - 12
M1 - e0003260
ER -