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

Abstract

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

EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases

“…Increasing numbers of investigators have recognized the importance of multivalent HFMD vaccines, which are mainly focused on EV-A71, CV-A16, CV-A6 and CV-A10. 75, 85, 86 Recently, a trivalent-inactivated EV-A71/CV-A16/CV-A6 vaccine showed good protection from lethal challenge against each homologous virus in mice, which was similar to that of the corresponding monovalent vaccine groups. 87 Moreover, a combination of formalin-inactivated EV-A71, CV-A6, CV-A10 and CV-A16 multivalent vaccine candidates could elicit serotype-specific neutralizing antibody responses in mice and rabbits, and no cross-neutralization efficacy was found among these viruses.…”

Molecular characterization of two novel echovirus 18 recombinants associated with hand-foot-mouth disease

“…Of these, CV-A16 and EV-A71 are the predominant etiologic agents. Other EV serotypes including CV-A2–6, CV-A8–10, CV-A12, CV-A14, CV-B1–6 and E-4–7, E-9, E-11, E-18, E-25, and E-30 were occasionally detected in sporadic cases or outbreaks of HFMD 19, 20 . Thus, persistent surveillance of HFMD pathogens might help to predict potential predominant serotypes and related disease outbreaks.…”

“…Thus, persistent surveillance of HFMD pathogens might help to predict potential predominant serotypes and related disease outbreaks. Recently CV-A6 and CV-A10 have been the prevalent etiologic agents in some provinces of China and in a few countries 19 . Although a vaccine for EV-A71 has been developed, it is important to develop multivalent vaccines against other main serotypes to protect children.…”

Ongoing change of severe hand, foot, and mouth disease pathogens in Yunnan, China, 2012 to 2016

“…The genus can be divided into 12 species: enteroviruses A‐J, and rhinoviruses A‐C comprising more than 100 types (http://www.picornaviridae.com/enterovirus/ev-b/ev-b.htm). enterovirus A71 (EV‐A71), coxsackievirus A16 (CV‐A16), and CV‐A6 are the three most common types in mainland China . Other EVs, CV‐A2–5, CV‐A8–A10, CV‐A12, CV‐A14, and CV‐B1–B6 and echoviruses (E)‐4 to 7, E‐9, E‐11, E‐18, E‐25, and E‐30 have been detected in sporadic cases or outbreaks of HFMD and frequently cocirculate with EV‐A71, CV‐A16, and CV‐A6 …”