Respiratory syncytial virus (RSV), an important pathogen causing lower respiratory tract infections in the elderly, has been the subject of continuous research and development for the production of effective and safe vaccines, both domestically and internationally. To date, three RSV vaccines have been approved for use globally, two recombinant protein subunit vaccines and an mRNA vaccine. As vaccines with different functional mechanisms, their efficacy and safety have yet to undergo systematic comparison and evaluation.

In this study, we sought to compare differences in the efficacy and safety of these RSV mRNA and recombinant protein subunit vaccines.

Computerized searches of the Web of Science, PubMed, Cochrane Library, Embase, and Scopus databases were conducted for randomized controlled trials (RCT) on the implementation of RSV vaccines in the population, with the search period extending from the date of database establishment to May 2025. The trial group consisted of individuals who received an injection of the RSV vaccine, whereas the control group received injection of a control vaccine. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the studies. Data analysis was conducted using R 4.5.0 and RevMan 5.4.1 software, and the evidence level of outcome measures was evaluated using the GRADE standard.

In terms of vaccine efficacy, mRESVIA was found to have highest protective effect based on Bayesian network meta-analysis [OR (95%CI) =0.17(0.09-0.31)], followed by Arexvy [OR (95%CI) =0.21(0.16-0.29)]. However, among the three vaccines, the protective efficacy of Abrysvo was relatively lower [OR (95%CI) =0.42(0.32-0.56)]. From the perspective of the level of immunogenicity, an independent sample t-test was conducted on the geometric mean ratio of antibody titers (GMFR) induced by the Arexvy vaccine and mRESVIA with the results indicating that in the RSV-B subgroup, the GMFR of Arexvy was significantly higher than that of mRESVIA, and the difference was statistically significant (t=-2.550, P=0.019). From the perspective of safety, a comparison of risk differences (RD) in the reporting rate of local (injection site) pain occurrence revealed that there was no statistically significant difference among the vaccines (P>0.05); a comparison of relative risks in the reported rates of serious adverse reactions/death events also showed that there was no statistically significant difference among the vaccines (P>0.05). Furthermore, the GRADE classification results revealed that the rates of lower respiratory tract infections, geometric mean fold rise, geometric mean ratio, and reporting of local (injection site) pain were of high-quality evidence, whereas in contrast, the reporting of severe/death events was of low-quality evidence.

Compared with traditional recombinant protein subunit vaccines, mRESVIA, an emerging mRNA vaccine, was found to have superior protective efficacy, which can be attributed to its unique advantages. We accordingly believe that this vaccine has considerable potential for future development and market expansion, although its long-term efficacy and protective effects for specific populations necessitate further verification.