ABSTRACT
Background: Given the paucity of data on safety and effectiveness of mRNA COVID-19 booster vaccinations in lower income settings with high HIV prevalence, we evaluated a heterologous mRNA-1273 (Moderna) boost after priming with 1 or 2 doses of Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine among health care workers (HCWs) in South Africa. Method(s): SHERPA is an open-label, phase 3 mRNA-1273 booster study, nested in the Sisonke Phase 3b implementation trial, that vaccinated ~500000 HCWs with 1 or 2 doses of Ad26.COV2.S from Feb and Dec 2021. Sisonke participants were offered mRNA-1273 boosters between 23 May and 12 Nov 2022 (median 17 and 8 months after 1 and 2 Ad26.COV2.S, respectively), with data cut-off on 12 Dec 2022. Reactogenicity and adverse events (AEs) were self-reported via an online data entry link shared by SMS with participants 1, 7 and 28 days after boosting. Using national databases analyses are underway to compare effectiveness against COVID-19 infections and severe disease with Sisonke participants who did not receive the booster. Result(s): 12188 HCWs (79.5% female, 28.6% with self-reported previous COVID-19 diagnosis) received a mRNA-1273 booster, of whom 44.6% and 55.4% had received 1 and 2 prior Ad26.COV2.S vaccines in Sisonke, respectively. 3056 (25.2%) reported being HIV positive, more among those receiving only 1 previous Ad26.COV2.S (26.8% vs 23.9%), and 1.4% reported not being on antiretroviral therapy. 17.0% of participants reported hypertension and 6.4% diabetes mellitus. 262 participants (2.1% of women, 2.5% of men) reported 234 reactogenicity events and 95 AEs post-vaccination, with more reported by those with prior COVID-19 infection (3.5% vs 1.6%), HIV negative status (2.5% vs 1.2%) and those who received 2 prior doses of Ad26.COV2.S (2.4% vs 1.8%) (Table). Among 159 (1.3%) reporting injection site reactions the commonest were pain (59.7%), swelling (42.1%) and induration (20.1%). Of 177 (1.5%) systemic reactogenicity events (all grade 1 or 2 severity), the commonest were myalgia (69.5%), headache (67.8%) and fever (37.9%). 14 participants had AEs of special interest or serious AEs, of which 4 (all AESIs of ageusia or anosmia) were deemed related to the booster. 13 COVID-19 infections occurred a median of 125 days post booster vaccination (IQR 90-154) after 3477 person-years of follow up. Conclusion(s): A mRNA-1273 booster administered after 1 or 2 doses of Ad26. COV2.S was well tolerated regardless of HIV status, other chronic conditions or prior COVID-19 infection.