Enterovirus 71 infection and vaccines

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Abstract

Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting young children during the spring to fall seasons. Recently, serious outbreaks of HFMD were reported frequently in the Asia-Pacific region, including China and Korea. The symptoms of HFMD are usually mild, comprising fever, loss of appetite, and a rash with blisters, which do not need specific treatment. However, there are uncommon neurological or cardiac complications such as meningitis and acute flaccid paralysis that can be fatal. HFMD is most commonly caused by infection with coxsackievirus A16, and secondly by enterovirus 71 (EV71). Many other strains of coxsackievirus and enterovirus can also cause HFMD. Importantly, HFMD caused by EV71 tends to be associated with fatal complications. Therefore, there is an urgent need to protect against EV71 infection. Development of vaccines against EV71 would be the most effective approach to prevent EV71 outbreaks. Here, we summarize EV71 infection and development of vaccines, focusing on current scientific and clinical progress.

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Clinical features, diagnosis, and management of enterovirus 71.

Mong How Ooi, See Chang Wong, Penny Lewthwaite … (2010)

Although poliomyelitis has been mostly eradicated worldwide, large outbreaks of the related enterovirus 71 have been seen in Asia-Pacific countries in the past 10 years. This virus mostly affects children, manifesting as hand, foot, and mouth disease, aseptic meningitis, poliomyelitis-like acute flaccid paralysis, brainstem encephalitis, and other severe systemic disorders, including especially pulmonary oedema and cardiorespiratory collapse. Clinical predictors of severe disease include high temperature and lethargy, and lumbar puncture might reveal pleocytosis. Many diagnostic tests are available, but PCR of throat swabs and vesicle fluid, if available, is among the most efficient. Features of inflammation, particularly in the anterior horns of the spinal cord, the dorsal pons, and the medulla can be clearly seen on MRI. No established antiviral treatment is available. Intravenous immunoglobulin seems to be beneficial in severe disease, perhaps through non-specific anti-inflammatory mechanisms, but has not been tested in any formal trials. Milrinone might be helpful in patients with cardiac dysfunction. Copyright © 2010 Elsevier Ltd. All rights reserved.

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Scavenger receptor B2 is a cellular receptor for enterovirus 71.

Seiya Yamayoshi, Yasuko Yamashita, Jifen Li … (2009)

Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China. Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.

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Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.

Xiaojuan Tan, Y. Hu, MingLei Zhang … (2014)

Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina. During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina. The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).

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Author and article information

Journal

Journal ID (nlm-ta): Clin Exp Vaccine Res

Journal ID (iso-abbrev): Clin Exp Vaccine Res

Journal ID (publisher-id): CEVR

Title: Clinical and Experimental Vaccine Research

Publisher: The Korean Vaccine Society

ISSN (Print): 2287-3651

ISSN (Electronic): 2287-366X

Publication date (Print): January 2017

Publication date (Electronic): 25 January 2017

Volume: 6

Issue: 1

Pages: 4-14

Affiliations

[1 ]Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon, Korea.

[2 ]Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Korea.

Author notes

Corresponding author: Sun-Young Chang, PhD. Laboratory of Microbiology, College of Pharmacy, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: +82-31-219-3454, Fax: +82-31-219-3435, sychang@ 123456ajou.ac.kr

Author information

Eun-Je Yi http://orcid.org/0000-0003-0947-7772

Yun-Ju Shin http://orcid.org/0000-0002-8106-6057

Jeong-Hwan Kim http://orcid.org/0000-0002-7481-0570

Tae-Gyun Kim http://orcid.org/0000-0002-1675-2253

Sun-Young Chang http://orcid.org/0000-0001-7336-9245

Article

DOI: 10.7774/cevr.2017.6.1.4

PMC ID: 5292356

PubMed ID: 28168168

SO-VID: 60090589-7902-413a-98d7-e8bdc92a6212

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 30 August 2016

Date revision received : 02 October 2016

Date accepted : 30 October 2016

Funding

Funded by: Ministry of Health and Welfare, CrossRef http://dx.doi.org/10.13039/501100003625;

Enterovirus 71 infection and vaccines

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Most cited references 79

Clinical features, diagnosis, and management of enterovirus 71.

Scavenger receptor B2 is a cellular receptor for enterovirus 71.

Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.

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