From Promise to Proof: Revealing the Comparative Performance of RSV Vaccines Through Network Meta-Analysis
DOI:
https://doi.org/10.53366/jimki.v12i2.1041Keywords:
Efficacy, Respiratory Syncytial Virus, Respiratory Illness, Vaccines, SafetyAbstract
Introduction: There is no consensus on the optimal vaccine platform for preventing respiratory syncytial virus (RSV) infection. Recent advances in RSV vaccine development aim to improve efficacy and safety across various platforms. This study aimed to compare the efficacy and safety of available RSV vaccines using a network meta-analytic approach to identify the most effective strategy for RSV prevention.
Methods: A systematic search of PubMed, ScienceDirect, Cochrane, and Scopus (up to November 2025) identified randomized controlled trials (RCTs) of RSV vaccines in healthy populations. Evaluated interventions included Ad26.RSV.preF–RSV preF, Ad26.RSV.preF, Bivalent RSVpreF, RSVPreF3OA, and placebo controls. Network meta-analyses were performed using the netmeta package in R. Risk of bias and certainty of evidence were appraised using RoB 2.0, CINeMA, and GRADE frameworks, respectively.
Result: Ten RCTs were analyzed. Ad26.RSV.preF–RSV preF Protein Vaccine possesses superior efficacy in reducing RSV-related respiratory illness compared to placebo (RR 0.25 [95% CI: 0.15-0.45]). Ranking analysis corroborated this finding, identifying it as the most effective intervention (P-score = 0.827). Safety profiles were comparable across all interventions; however, the precision of these estimates was limited by wide confidence intervals and substantial heterogeneity.
Conclusion: Ad26.RSV.preF–RSV preF demonstrated the highest efficacy for RSV prevention. However, their safety profile has not yet been clearly defined, and further research is needed to assess long-term effectiveness and monitor potential late adverse effects.
References
1. Li Y, Wang X, Blau DM, Caballero MT, Feikin DR, Gill CJ, Madhi SA, Omer SB, Simões EAF, Campbell H, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 2022;399(10340):2047–64.
2. Langedijk AC, Bont LJ. Respiratory syncytial virus infection and novel inter- ventions. Nat Rev Microbiol 2023.
3. Anastassopoulou, C.; Medi´c, S.; Ferous, S.; Boufidou, F.; Tsakris, A. Development, Current Status, and Remaining Challenges for Respiratory Syncytial Virus Vaccines. Vaccines 2025, 13, 97. https://doi.org/ 10.3390/vaccines13020097
4. WHO. 2025. WHO position paper on immunization to protect infants against respiratory syncytial virus disease, May 2025. Weekly Epidemiological Record, 100(22), 193–218.
5. Pang Y, Lu H, Cao D, Zhu X, Long Q, Tian F, Long X, Li Y. Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis. BMC Public Health. 2024 May 6;24(1):1244. doi: 10.1186/s12889-024-18748-8. PMID: 38711074; PMCID: PMC11075318.
6. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med [Internet]. 2015 Jun 2 [cited 2025 Apr 17];162(11):777–84. Available from: https://pubmed.ncbi.nlm.nih.gov/26030634/
7. Cochrane Handbook for Systematic Reviews of Interventions | Cochrane [Internet]. [cited 2025 Sep 23]. Available from: https://www.cochrane.org/authors/handbooks-and-manuals/handbook
8. WHO. “Respiratory Syncytial Virus (RSV).” Who.int, World Health Organization: WHO, 3 Feb. 2025, www.who.int/news-room/fact-sheets/detail/respiratory-syncytial-virus-(rsv).
9. Minasian, Lori M, et al. “Clinician and Patient Reporting of Symptomatic Adverse Events in Cancer Clinical Trials: Using CTCAE and PRO-CTCAE® to Provide Two Distinct and Complementary Perspectives.” Patient Related Outcome Measures, vol. Volume 13, Dec. 2022, pp. 249–258, https://doi.org/10.2147/prom.s256567.
10. J.J. Allaire. RStudio: Integrated Development for R. 2022;1. Available from: http://www.rstudio.com/.
11. Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. BMJ Ment Heal [Internet]. 2019 Oct 23 [cited 2025 Apr 17];22(4):153–60. Available from: https://mentalhealth.bmj.com/content/22/4/153
12. Rücker G, Schwarzer G. Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol [Internet]. 2015 Jul 31 [cited 2025 Apr 17];15(1):1–9. Available from: https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-015-0060-8
13. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ [Internet]. 2019 Aug 28 [cited 2025 Apr 17];366. Available from: https://www.bmj.com/content/366/bmj.l4898
14. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods [Internet]. 2021 Jan 1 [cited 2024 Aug 15];12(1):55–61. Available from: https://pubmed.ncbi.nlm.nih.gov/32336025/
15. Balduzzi S, Rücker G, Nikolakopoulou A, Papakonstantinou T, Salanti G, Efthimiou O, et al. netmeta: An R Package for Network Meta-Analysis Using Frequentist Methods. J Stat Softw [Internet]. 2023 Mar 23 [cited 2025 Apr 17];106(2):1–40. Available from: https://www.jstatsoft.org/index.php/jss/article/view/v106i02
16. Wickham, H. and Bryan, J. (2019) Readxl Read Excel Files R Package Version 1.3.1. - References - Scientific Research Publishing [Internet]. [cited 2025 Apr 17]. Available from: https://www.scirp.org/reference/referencespapers?referenceid=2761680
17. Henson R, Friston K. Convolution models for fMRI. Stat Parametr Mapp Anal Funct Brain Images. 2007;178–92.
18. Dahiru T. P – VALUE, A TRUE TEST OF STATISTICAL SIGNIFICANCE? A CAUTIONARY NOTE. Ann Ibadan Postgrad Med [Internet]. 2008 Mar 3 [cited 2025 Apr 17];6(1):21. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4111019/
19. Nikolakopoulou A, Higgins JPT, Papakonstantinou T, Chaimani A, Giovane C Del, Egger M, et al. CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLoS Med [Internet]. 2020 Apr 2 [cited 2025 Apr 17];17(4). Available from: https://pubmed.ncbi.nlm.nih.gov/32243458/
20. Papakonstantinou T, Nikolakopoulou A, Higgins JPT, Egger M, Salanti G. CINeMA: Software for semiautomated assessment of the confidence in the results of network meta-analysis. Campbell Syst Rev [Internet]. 2020 Mar 1 [cited 2025 Apr 17];16(1):e1080. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/cl2.1080
21. Izcovich A, Chu DK, Mustafa RA, Guyatt G, Brignardello-Petersen R. A guide and pragmatic considerations for applying GRADE to network meta-analysis. BMJ [Internet]. 2023 Jun 27 [cited 2025 Apr 17];381. Available from: https://www.bmj.com/content/381/bmj-2022-074495
22. Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook [Internet]. 2013 [cited 2025 Sep 23]. Available from: https://gdt.gradepro.org/app/handbook/handbook.html
23. Falsey AR, Williams K, Gymnopoulou E, Bart S, Ervin J, Bastian AR, et al. Efficacy and safety of an Ad26.RSV.preF–RSV preF protein vaccine in older adults. N Engl J Med. 2023;388:609-20.
24. Falsey AR, Hosman T, Bastian AR, Vandenberghe S, Chan EKH, Douoguih M, et al. Long-term efficacy and immunogenicity of Ad26.RSV.preF–RSV preF protein vaccine (CYPRESS): phase 2b trial. Lancet Infect Dis. 2024;24:1015-24.
25. Ison MG, Papi A, Athan E, Feldman RG, Langley JM, Lee DG, et al. Efficacy and safety of RSVPreF3 OA in older adults over two RSV seasons. Clin Infect Dis. 2024;78:1732-44.
26. Ison MG, Papi A, Athan E, Feldman RG, Langley JM, Lee DG, et al. Efficacy, safety, and immunogenicity of RSVPreF3 OA over three RSV seasons (AReSVi-006). Lancet Respir Med. 2025;13:517-29.
27. Papi A, Ison MG, Langley JM, Lee DG, Leroux-Roels I, Martinon-Torres F, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388:595-608.
28. Sadoff J, De Paepe E, DeVincenzo J, Gymnopoulou E, Menten J, Murray B, et al. Prevention of RSV infection by Ad26.RSV.preF in a human challenge study. J Infect Dis. 2022;226:396-406.
29. Schmoele-Thoma B, Zareba AM, Jiang Q, Maddur MS, Danaf R, Mann A, et al. Vaccine efficacy in adults in an RSV challenge study. N Engl J Med. 2022;386:2377-86.
30. Stuart ASV, Virta M, Williams K, Seppa I, Hartvickson R, Greenland M, et al. Phase 1/2a safety and immunogenicity of Ad26.RSV.preF in adults and seropositive children. J Infect Dis. 2023;227:71-82.
31. Tamura H, Momose A, Takato Y, Richuan Z, Bastian AR, Callendret B, et al. Phase 3 study of Ad26.RSV.preF/RSV preF vaccine in Japanese adults. Respir Investig. 2025;63:560-8.
32. Walsh EE, Pérez Marc G, Zareba AM, Falsey AR, Jiang Q, Patton M, et al. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med. 2023;388:1465-77
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