Effect of Platform Type on Clinical Efficacy of SARS-CoV-2 Vaccines in Prime Vaccination Settings: A Systematic Review and Meta-Regression of Randomized Controlled Trials

Abstract

This systematic review investigated the association between platform type and the clinical efficacy of SARS-CoV-2 vaccines using the meta-regression of randomized controlled trials to compare the rates of the first appearance of symptomatic COVID-19 on the platforms. The trial search was conducted using PubMed, ClinicalTrials.gov, and the EU Clinical Trials Register. The main selection criteria included: non-active control, immunocompetent individuals without previous vaccination, and a low risk of bias. The platform effect was summarized with an incidence rate ratio (IRR) and a 95% confidence interval for every platform category against the reference. IRR was obtained by random-effect meta-regression with adjustment for confounding by effect modifiers. The analysis was conducted in per-protocol (PP) and modified intention-to-treat (mITT) sets. Six vaccine types with 35 trials were included. Vector vaccines were a reference category. In the PP set, rates of symptomatic COVID-19 on mRNA and protein subunit vaccines were significantly lower than on the vector: IRR = 0.30 [0.19; 0.46], p = 0.001 and 0.63 [0.46; 0.86], p = 0.012, respectively. There was no difference for inactivated and virus-like particle vaccines compared to the vector: IRR = 0.98 [0.71; 1.36], p = 0.913 and 0.70 [0.41; 1.20], p = 0.197, respectively. The rate of cases on DNA vaccines was significantly higher than that on the vector: IRR = 2.58 [1.17; 5.68], p = 0.034. Results for the mITT set were consistent. Platform type is an effect modifier of the clinical efficacy of SARS-CoV-2 vaccines.