Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) have caused severe epidemics of
hand, foot and mouth disease (HFMD) in the Asia Pacific in recent years, particularly in infants and young children. This disease has become a serious public health problem, as no
vaccines or
antiviral drugs have been approved for EV71 and CA16
infections. In this study, we compared four monovalent
vaccines, including
formalin-inactivated EV71 virus (iEV71), EV71 virus-like particles (VLPs) (vEV71),
formalin-inactivated CVA16 virus (iCVA16) and CVA16 VLPs (vCVA16), along with two
bivalent vaccines, including equivalent doses of
formalin-inactivated EV71+CVA16 virus (iEV71+iCVA16) and EV71+CVA16 VLPs (vEV71+vCVA16). The
IgG titers and neutralization
antibodies titers demonstrated that there are no immune interference exists between the two immunogens of EV71 and CVA16.
IgG subclass isotyping revealed that
IgG1 and
IgG2b were induced primarily in all
vaccine groups. Furthermore, cross-neutralization
antibodies were elicited in mouse sera against other sub-genotypes of EV71 and CVA16. In vivo challenge experiments showed that the
immune sera from vaccinated animals could confer passive protection to newborn mice against lethal challenge with 14 LD50 of EV71 and 50 LD50 of CVA16. Our results indicated that bivalent vaccination is promising for HFMD
vaccine development. With the advantage of having a better safety profile than inactivated virus
vaccines, VLPs should be used to combine both EV71 and CVA16
antigens as a candidate
vaccine for prevention of HFMD virus transmission.