5. Conclusions
coinfections
Whilst we previously showed that shedding of challenge ORV dose was significantly reduced among P2-VP8 vaccine recipients compared to placebo, we did not find any association between serum RV-specific immune responses measured one month post-P2-VP8 vaccination and fecal shedding of RV post-challenge. Lack of significance observed could be a result of a limited sample size and additional investigations with increased sample size are required. However, these data may also suggest that the identification of a serological correlate of protection for an injectable subunit rotavirus vaccine may require greater dissection of the immune responses elicited by vaccination. This may include further investigation of the response by IgG subclass, and evaluating cellular Fc effector functions, for example antibody (Ab)-dependent cellular phagocytosis, activated when the Ab Fc region forms immune complexes with antigens and Fc receptors on innate immune cells. In the absence of an absolute immunological correlate of protection for RV, it is difficult to establish the usefulness of this fecal shedding model using only immunological correlations. In order to clearly establish whether shedding post-ORV challenge can be used as a marker of field efficacy, further studies are needed to investigate whether fecal shedding post-ORV challenge is correlated with clinical protection. In addition, any evaluation of shedding needs to take other potential confounders into account, including Lewis and secretor status, breastmilk antibodies, and presence of enteric coinfections at the time of vaccination.