The rotavirus cVLPVP8∗ vaccine candidate induces cross-genotype/heterotypic neutralizing antibody responses against human rotavirus G9P[4].

Live oral rotavirus (RV) vaccines show variable efficacy and safety profiles, particularly in low- and middle-income countries (LMICs). We have developed a chimeric hepatitis B core parenteral virus-like particle displaying VP8∗P[8] RV vaccine antigen (cVLPVP8∗) capable of inducing VP8∗- specific serum neutralizing antibodies (nAbs). The immunogenicity of cVLPVP8∗ and its potential to induce cross-genotype/heterotypic nAbs was investigated following subcutaneous administration of low, medium, and high doses in mice. The cVLPVP8∗ vaccine elicited potent VP8∗-specific humoral responses, including serum IgG, IgA, as well as nAbs. Strong IgG and also IgA responses were detected after the third immunization, highlighting the importance of booster vaccine doses. All tested antigen doses elicited detectable cross-nAbs against the heterotypic G9P[4] RV strain, supporting the possibility of antigenic relatedness between the VP8∗P[8] vaccine antigen and the P[4] genotype within the P[II] genogroup. Moreover, the high-dose group induced significantly higher cross-nAb titers compared with the low-dose group, indicating that increased antigen dosage enhances nAb responses. Overall, mice vaccinated with the cVLPVP8∗ vaccine based on a P[8] genotype developed serum antibodies that neutralized a RV strain from genotype P[4] in this study and a more divergent virus from genotype P[2] in our earlier work indicating that the vaccine has potential for generating neutralization breadth.