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Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development.

ABSTRACT: Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen's genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection and the circulation of different genetic strains of EV-A71 virus has been identified around the world. In this review, we present and discuss the molecular epidemiology and pathogenesis of the human disease caused by EV-A71 infection, as well as current prospects for the development of an EV-A71 vaccine.

SUBMITTER: Chang YK

PROVIDER: S-EPMC6223252 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development.

Chang Yu-Kang YK Chen Kou-Huang KH Chen Kow-Tong KT

Revista do Instituto de Medicina Tropical de Sao Paulo 20181108

Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen's genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection an ...[more]

PMID: 30427405

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Project description:UnlabelledEnterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia.ImportanceEV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study, we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus.

Project description:Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-γ T cells associated with Th1/Th2-balanced IFN-ɣ, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-γ T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune responses against CV infection.

Dataset Information

Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development.

Publications

Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development.

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