Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis

Abstract Background: Dose fractionation of Coronavirus Disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.Methods: We systematically reviewed clinical trials reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T-cell responses and safety profiles between fractional and standard dose groups.Results: We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2 specific nAbs and T-cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.Conclusion: Dose fractionation of mRNA and protein subunit vaccines may be safe and effective.