Respiratory syncytial virus (RSV) poses a substantial global health threat. Most individuals have been infected with RSV at least once prior to vaccination, resulting in the presence of pre-existing antibodies. In this study, Balb/C mice were either pre‑exposed or non-pre-exposed to RSV on day 0, followed by a two-dose regimen of an RSV subunit vaccine on days 28 and 56. Two prefusion RSV F proteins (Pre-F-1 and Pre-F-2) were designed as vaccine antigens, formulated with Alum + CpG adjuvant to promote a Th1-biased response. Results showed that once pre-exposed to RSV (PC group), a robust immune activation was induced in the mice. Compared with the non-pre-exposed control (nPC group), the PC group exhibited a continued rise of postfusion-F (post-F)-specific IgG binding titers and neutralizing antibody (nAbs) against RSV A2 over 77 days, leading to a reduced lung viral load upon rechallenge. However, the PC group also showed greater weight loss and higher lung histopathological scores (HPS). In pre-exposed mice, a single vaccine dose steadily increased both binding titers and nAbs, while a two-dose regimen reversed the post-F/pre-F ratio and slightly lowered pulmonary viral load. In non-pre-exposed mice, two-doses of vaccination increased binding titers and nAbs, reduced weight loss, and significantly decreased lung viral load. This study highlights the importance of prior RSV infection status in designing and clinically translating adjuvanted subunit RSV vaccines. Our results indicate that in pre-exposed Balb/C mice, high preexisting post-F titers can affect subsequent vaccine immune responses and protective efficacy. This study also demonstrates that the immunological background of whether mice have been pre-exposed with RSV can significantly influence the evaluation of RSV subunit vaccine immunogenicity and protective efficacy.
Keywords: Alum + CpG; RSV; pre‐F; prime infection; subunit vaccine.
PMID: 42132475
DOI: 10.1002/jmv.70971
