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Introduction: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. Methods: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. Results: mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P< 0.0001; I2= 66.8%] and higher total antibody titers [relative increase, 50.45% (95% CI, 34.63%, 66.28%); P< 0.0001; I2= 89.5%] versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. Conclusion: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients.

Introduction: The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. Methods: We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19–related hospitalization, and COVID-19–related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. Results: Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19–related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19–related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2> 75%) except death (I2= 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. Conclusion: Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years.