Is a multivalent hand, foot, and mouth disease vaccine feasible?

Abstract

Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

Keywords: EV-A71 vaccine; bivalent and multivalent vaccines; coxsackievirus A16; coxsackieviruses B3 and B5; echovirus 30; enterovirus A (EV-A); enterovirus A71; epidemiology; foot and mouth diseases; hand; inactivated whole virion vaccines; monovalent.

Figure 1.

Geographical distribution of enterovirus A71 genotypes and subgenotypes during outbreaks from 1997 to 2013. The figure is an up-dated compilation of tables and data published in refs. . EU includes the Netherlands, Denmark, the United Kingdom, Germany, France and Austria.