Review of Enterovirus 71 Vaccines

Chong, Pele; Liu, Chia-Chyi; Chow, Yen‐Hung; Chou, Ai-Hsiang; Klein, Michel

doi:10.1093/cid/ciu852

Cited by 132 publications

(110 citation statements)

References 36 publications

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“…Based on VP1 gene phylogenetic studies, EV-A71 has now been classified into 6 genotypes, A to F. 72,119 Genotype A contains only the prototypic strain BrCr/1970. Genotypes B and C have been further divided into 6 and 5 sub-genotypes, B0-B5 and C1-C5, respectively.…”

Section: Molecular Epidemiologymentioning

confidence: 99%

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

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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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.

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Section: Molecular Epidemiologymentioning

confidence: 99%

“…9 In the absence of approved antiviral treatment, 71 a multivalent prophylactic vaccine against HFMD is urgently needed and the development of an efficacious EV-A71 vaccine in particular has been a national health priority in some Asian countries. 72 …”

Section: Introductionmentioning

confidence: 99%

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

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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“…Genotypes B3, B4, B5, C1, C2, C4 and C5 contributed to recent outbreaks [129]. Interestingly, cross-neutralization of different genotypes by immune sera from animals and humans is limited, indicating that EV-A71 became antigenically diverse [130][131][132].…”

Section: Neutralization Of Picornaviruses Neutralization Of Ev-a71 Anmentioning

confidence: 99%

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

Anastasina

Domanska

Palm

et al. 2017

Journal of General Virology

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Picornaviruses are the most commonly encountered infectious agents in mankind. They typically cause mild infections of the gastrointestinal or respiratory tract, but sometimes also invade the central nervous system. There, they can cause severe diseases with long-term sequelae and even be lethal. The most infamous picornavirus is poliovirus, for which significant epidemics of poliomyelitis were reported from the end of the nineteenth century. A successful vaccination campaign has brought poliovirus close to eradication, but neurological diseases caused by other picornaviruses have increasingly been reported since the late 1990s. In this review we focus on enterovirus 71, coxsackievirus A16, enterovirus 68 and human parechovirus 3, which have recently drawn attention because of their links to severe neurological diseases. We discuss the clinical relevance of these viruses and the primary role of humoral immunity in controlling them, and summarize current knowledge on the neutralization of such viruses by antibodies.

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“…[1][2][3] In the past 10 y, outbreaks and epidemic caused by EV71 have occurred more frequently, which has emerged as a serious threat to public health, especially in the Asia-Pacific region. [4][5][6][7] EV71 is now considered as the most dangerous neurotropic enterovirus of the post-polio era. 8,9 Currently, 3 inactivated EV71 vaccines developed in China have demonstrated good efficacy and safety profile in the phase 3 clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6-35 months

Jin

Zhang

et al. 2016

Human Vaccines & Immunotherapeutics

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Background: A primary goal of this study was to establish the serological mechanistic correlate of protection (mCoP) for an inactivated Enterovirus 71 (EV71) vaccine. Methods: We used the Prentice criterion framework and scaled logit model to explore the relationship between the neutralizing antibody (NTAb) and EV71-associated disease, and to build a protection curve for estimating the efficacy of EV71 vaccine. Data of NTAb at day 56 post-vaccination and the occurrence of EV71-associated disease during a 12-month follow-up period were collected from a phase 3 efficacy trial of EV71 vaccine in this study.Results: NTAb at day 56 post-vaccination in participants met the Prentice criterion framework. According to the protection curve, the antibody levels of 14.7, 27.8, 55.7, 129.0 and 459.4 (U/mL) were associated with 50%, 60%, 70%, 80% and 90% clinical protection rate, respectively. Vaccine efficacy predicted by the model was 81.5%, which was very similar to the actual vaccine efficacy of 80.4% (95% CI, 58.2, 90.8) observed in the phase 3 trial. Conclusions: NTAb titers post-vaccination can be validated as mCoP for evaluating the efficacy of an inactivated enterovirus 71 vaccine, with a titers of 14.7 (U/ml) as a surrogate associated with the protection of 50% against EV71-associated disease.

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Review of Enterovirus 71 Vaccines

Cited by 132 publications

References 36 publications

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

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

Human picornaviruses associated with neurological diseases and their neutralization by antibodies

Validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6-35 months

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