The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking. METHODS: This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as "Respiratory Syncytial Virus, Human," "Respiratory Syncytial Virus Infections," "Respiratory Syncytial Virus Vaccines," "Immunization," "Immunization Programs" and "Vaccines" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. RESULTS: Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. CONCLUSION: LID M2-2, MEDI M2-2, RSVcps2 and LID/M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.