EV71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines

Klein, Michel

doi:10.1586/14760584.2015.993385

Cited by 23 publications

(13 citation statements)

References 24 publications

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“…It is also the first step toward the development of multivalent HFMD vaccines. 134 Recent EV-A71 vaccine development Several EV-A71 candidate vaccines are still at the pre-clinical stage. 72,135,136 Synthetic vaccines based on immunodominant linear neutralization epitopes are safe, cost-effective, but poorly immunogenic even when formulated with Freund's adjuvants.…”

Section: Ev-a71 Vaccines: the First Step Toward Multivalent Hfmd Vaccmentioning

confidence: 99%

“…Based on epidemiological data, we propose that the first step should be to generate a tetravalent vaccine containing EV-A71, CV-A16, CV-A6 and CV-A10 134,175 to cover the most prevalent HFMD pathogens, then to further incorporate CV-B3, CV-B5 and E-30 immunogens in a heptavalent vaccine to prevent the risks of aseptic meningitis and acute myocarditis associated with these viruses in the course of multi-serotype HFMD epidemics. 134 The addition of CV-A4 and CV-A5 components should not be considered at this stage since they are essentially responsible for HA outbreaks.…”

Section: Development Of a Bivalent Ev-a71/cv-a16 Vaccinementioning

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: Ev-a71 Vaccines: the First Step Toward Multivalent Hfmd Vaccmentioning

confidence: 99%

Section: Development Of a Bivalent Ev-a71/cv-a16 Vaccinementioning

confidence: 99%

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

Klein¹,

Chong

2015

Human Vaccines & Immunotherapeutics

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“…Among these enteroviruses, enterovirus 71 (EV71) and coxsackievirus A16 (CA16) had been responsible for majority of the HFMD outbreaks before 2008 (Mao et al, 2014;Wong et al, 2010) and therefore have been targeted for vaccine development (Chong et al, 2015;Klein, 2015;Liu et al, 2014Liu et al, , 2015Mao et al, 2014). However, clinical surveillance data show that coxsackievirus A6 has emerged as one of the major causative agents of HFMD since 2009 (Bian et al, 2015).…”

mentioning

confidence: 99%

Yeast-produced recombinant virus-like particles of coxsackievirus A6 elicited protective antibodies in mice

et al. 2016

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“…Due to a lack of effective treatment options, controlling EV71 epidemics has predominantly relied upon the formation of EV71 vaccines (11). Therefore, effective vaccines that protect against EV71-associated HFMD or herpangina are important (25). Currently, two monovalent EV71 vaccines have been marketed in mainland China (2).…”

Section: Discussionmentioning

confidence: 99%

Enterovirus 71 infection impairs the reproductive capacity of female mice

Qin

Yan

Chen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD); however, no clinically approved vaccine or antiviral treatment is currently available for EV71 infection. In the present study, a murine model of EV71 infection was constructed. The clinical isolates of EV71 were amplified in Vero cells and used to challenge adult mice via hydrodynamic injection (HI) and intraperitoneal injection (IP). Following two challenges, >50% of the mice succumbed to EV71 infection. Surviving female mice were identified to have impaired fertility and their litter sizes were significantly decreased compared with the control group. The antibody against EV71-VP1 persisted in the sera of female mice at a high titer for >2 years after challenge. The maternal antibody in the offspring sera also persisted for ~1 year and disappeared after ~2 years. Results from the present study suggest that a high titer of active EV71 was able to impair the reproductivity of adult female mice, and that high levels of maternal antibody persisted in the offspring and protected postnatal mice from EV71-induced mortality. The promising antigenicity, immunogenicity and reactogenicity of EV71 suggests that it a potential vaccine target that may be beneficial to the control of HFMD, through immunizing infants and women of reproductive age. IntroductionEnterovirus (EV) 71 is a member of the picornaviridae family of viruses that contain single-stranded positive-sense RNA (1), which primarily infects children <5 years old (2). Infants with EV71 infection develop sores on their hands, feet, buttocks and mouth; therefore, the infection is referred to as hand, foot and mouth disease (HFMD) (3). Several types of enterovirus have been indicated to cause HFMD in children; however, EV71 is commonly associated with severe complications of the nervous system in infants with HFMD and is therefore considered to be a major virulent pathogen and cause of mortalities in HFMD (4). Previous studies have indicated that a total of 488,955 HFMD cases and 126 HFMD-associated mortalities were reported in 2008 in China, of which EV71 infection was the primary cause (5). EV71 is a non-enveloped virus with a single-stranded positive-sense RNA genome that is ~7.5 kb in size and belongs to the enterovirus genus of the picornaviridae family (6). EV71 is classified into five genotypes as follows: A, B, C, D and F, and further subdivided into B0-B5 and C1-C5 subgenotypes (7). HFMD is an important public health issue and further understanding of the mechanisms underlying the development of HFMD are required to develop effective treatments. In mainland China, Taiwan and Singapore, EV71 whole-virus vaccines have been produced by various manufacturers. Two available inactivated EV71 vaccines have been approved by the China Food and Drug Administration, one produced by Sinovac Biotech Ltd. and the other by the Chinese Academy of Medical Science (all Beijing, China) (8-10). Currently, no effective treatment is available to treat severe EV71 infections, aside from symp...

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EV71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines

Cited by 23 publications

References 24 publications

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

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

Yeast-produced recombinant virus-like particles of coxsackievirus A6 elicited protective antibodies in mice

Enterovirus 71 infection impairs the reproductive capacity of female mice

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