Efficacy, Immunogenicity, and Safety of COVID-19 Vaccines in Randomized Control Trials in the Pre-Delta Era: A Systematic Review and Network Meta-Analysis

Abstract

The most effective method of limiting the coronavirus disease pandemic of 2019 (COVID-19) is vaccination. For the determination of the comparative efficacy and safety of COVID-19 vaccines and their platforms during the pre-Delta era, a systematic review and network meta-analysis was conducted. The MEDLINE, Embase, and MedRxiv databases were searched, and the gray literature was manually searched up to 8 July 2021. The review includes the phase II and III randomized controlled trials (RCTs) that assessed the efficacy, immunogenicity, and safety of the COVID-19 vaccines. The network meta-analysis used a Bayesian model and used the surface under the cumulative ranking to rank the comparisons between the vaccines. All included studies were quality appraised according to their design, and the heterogeneity of the analyses was assessed using I2. In terms of vaccine efficacy, the mRNA-1273 vaccine ranked the highest, and the CoronaVac vaccine ranked the lowest. The mRNA-1273 ranked the highest for neutralizing antibody responses to live SARS-CoV-2. The WIV04 vaccine was associated with the lowest incidence of both local and systemic adverse reactions. All studies except one had a low to moderate risk of bias. The mRNA platform vaccines showed higher efficacy and more adverse reactions than the other vaccines.

Reinfection rates, change in antibody titers and adverse events after COVID-19 vaccination among patients previously infected with COVID-19 in Metro Manila, Philippines: a secondary analysis of a completed cohort study

“…In this study, adverse events following immunization were more frequently reported among mRNA and viral vector vaccines compared to inactivated virus vaccines. This finding is consistent with other studies [ 6 , 20 ]. Increased vaccine reactogenicity has been associated with higher post-vaccination antibody levels [ 21 ].…”

“…Another network meta-analysis published in 2022 demonstrated that mRNA-1273 resulted in the largest increase in neutralizing antibodies levels (SMD 1,605.34, 95% CI 1,534.68, 1,676.00). Only mRNA-1273 had significantly increased risk of systemic adverse reactions compared to placebo (RR 6.69, 95% CI 3.82, 11.71) [ 6 ].…”

Quantitative Benefit–Risk Assessment of COVID-19 Vaccines Using the Multi-Criteria Decision Analysis

“…In a previous network meta-analysis, mRNA-1273 and BNT162b2 were significantly better than placebo in VE, whereas the effect of Ad26.COV.2. was not significant [47]. This was consistent with the trend in the benefit scores in this study.…”

Humoral Response after a Fourth Dose with mRNA-1273 in Healthcare Workers with and without a History of SARS-CoV-2 Infection and Previously Vaccinated with Two Doses of BBIBP-CorV Plus BNT162b2 Vaccine

“…All these vaccines have proven effective and were used in different parts of the world according to availability. However, vaccines based on messenger ribonucleic acid (mRNA) platforms have shown greater efficacy and higher neutralizing antibody (NAbs) responses than other vaccine platforms, including inactivated vaccines [4]; also, it has been reported that heterologous vaccination schemes Vaccines 2023, 11, 894 2 of 13 can potentiate a more significant immune response than homologous vaccination [5]. The level of neutralizing antibodies reflects the immunogenicity elicited by vaccines and has been used to predict the efficacy of vaccines against COVID-19 [6,7].…”