Enterovirus 71 (EV71) is the causative agent of Hand Foot and Mouth disease in paediatrics and can present with severe neurological complications. Epidemics in the Asian-Pacific regions have prompted the need for vaccination strategies. Most synthetic peptide vaccination strategies aimed at Enterovirus 71 (EV71) have focused on the induction of a protective humoral immune response. However, the induction of a functional cellular immune response is imperative for viral clearance and the initiation of a cognate anti-EV71 CD8+ help.
Although human CD4+ responses to EV71 infections have been documented, only recently have they involved the computational identification and validation of T-cell epitopes. Computational methods for predicting and modelling epitopes have improved but there still remains an Achilles heel in CD4+ epitope prediction algorithms due to the degree of polymorphism on the MHC II. For broad population recognition, an epitope must contain conservation against considerable MHC diversity.
The aim of this study was to evaluate whether computational algorithms can successfully identify CD4 epitopes. We first tested this theory in mice and expanded it to test human responses. Our results in mice showed that immune-dominant peptides were presented to T-cells. Three peptides induced broad immune responses to peptide-stimulated whole blood from 13 out of 20 human volunteers studied, of multiple human HLA-DR and HLA-DQ types. Two peptides that stimulated murine (H-2b) and (H-2d)in our previous work also induced the production of IFN-y in our human participants.
This study demonstrates the usefulness of a computationally assisted vaccination strategy. The broad recognition of the peptide epitopes further empathises the potential for use as a vaccine candidate against EV71.