Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines

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Abstract

Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family, which also includes viruses such as polioviruses. EV71, together with coxsackieviruses, is widely known for its association with Hand Foot Mouth Disease (HFMD), which generally affects children age five and below. Besides HFMD, EV71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. Considering the lack of a vaccine and antiviral drug against EV71, together with the increasing spread of these viruses, the development of such drugs and vaccines becomes the top priority in protecting our younger generations. This article, hence, reviews some of the recent progress in the formulations of anti-therapeutics and vaccine generation for EV71, covering (i) inactivated vaccines; (ii) baculovirus-expressed vaccines against EV71; (iii) human intravenous immunoglobulin (IVIg) treatment; and (iv) the use of monoclonal antibody therapy as a prevention and treatment for EV71 infections.

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An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.

Monto Ho, Eng-Rin Chen, Kwo-Hsiung Hsu … (1999)

Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died. We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health. The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died. Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.

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An apparently new enterovirus isolated from patients with disease of the central nervous system.

N J Schmidt, E H Lennette, H. H. Ho (1974)

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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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Contributors

George Belov: Role: Academic Editor

Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 08 December 2015

Publication date Collection: December 2015

Volume: 7

Issue: 12

Pages: 6441-6457

Affiliations

[1 ]Animal Health Biotechnology, Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604; qingyong@ 123456tll.org.sg

[2 ]College of Animal Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310013, China

[3 ]Department of Microbiology Faculty of Medicine, National University of Singapore, Singapore 117604

Author notes

[* ]Correspondence: hefang@ 123456tll.org.sg (F.H.); kwanghs@ 123456163.com (J.K.); Tel.: +65-68727470 (F.H.); +65-68727473 (J.K.); Fax: +65-68727007 (J.K.)

Article

Publisher ID: viruses-07-02949

DOI: 10.3390/v7122949

PMC ID: 4690872

PubMed ID: 26670245

SO-VID: fea14f55-7b70-4d36-ba89-cc366c4d75b8

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This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines

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Abstract

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MDPI: Coronavirus

Most cited references 100

An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.

An apparently new enterovirus isolated from patients with disease of the central nervous system.

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

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