Development and Immunogenicity Evaluation of an RSV Recombinant Vaccine Displaying a Conserved Domain of RSV G

Respiratory syncytial virus (RSV) causes severe lung infections in infants and the elderly. The conserved central domain (CCD) of the RSV G protein is a key antigenic fragment for inducing protective antibodies. In this study, we used the hepatitis B surface antigen (HBsAg) as a platform to present this RSV G CCD fragment.

We first sequenced and compared several HBsAg genotypes from clinical samples and selected one as an expression candidate for further development. The RSV G CCD was then inserted into the selected candidate to generate a recombinant expression construct. Subviral particles (SVPs) were produced using both CHO cells and yeast expression systems. Particle assembly was examined using electron microscopy. Finally, the safety and immunogenicity of the recombinant vaccine were evaluated in mice.

We successfully identified HBsAg38 as a potential recombinant vaccine expression candidate due to its abundant expression and secretion. The RSV G CCD fragment was inserted into the candidate and efficiently expressed in both CHO cells and yeast. The expressed protein was effectively secreted and formed uniform, spherical particles. The resulting vaccine candidate was safe for mice, causing no detectable weight loss or organ damage. Immunization with the recombinant SVPs elicited antibody responses against both HBsAg and the RSV G CCD. Upon intranasal RSV challenge, vaccinated mice exhibited markedly reduced RSV F protein and mRNA levels in lung tissues compared to PBS controls, with the yeast-derived SVP group showing the most pronounced reduction. Histopathological analysis further revealed that immunized mice had significantly less alveolar destruction and inflammatory cell infiltration than the control group, confirming that the vaccine conferred effective protection against RSV-induced lung pathology.

We successfully developed a novel antigen-displaying HBsAg platform for generating vaccines targeting multiple pathogens. The RSV G CCD-expressing HBsAg induced a strong antibody response and provided effective protection against RSV infection. This platform offers a promising new approach for the development of next-generation vaccines.