Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections

Jiangning Liu,Jing Wu,Yongdong Liu,Ling Xue,Binbin Zhao,Chuan Qin,Yanfeng Xu

doi:10.1186/s12985-020-01328-8

Abstract

BackgroundProphylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection.MethodsTo evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured.ResultsThe high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization.ConclusionsThe present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.

Highlights

Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection
Various EV71 vaccines have been developed, and since 2015 three EV71 vaccines have been approved by Chinese FDA to prevent the continuous epidemics [14,15,16], which were separately developed by Institure of Medical Biology, Chinese Academy of Medical Sciences (CAMS, Kunming Institute), Sinovac Biotech Co., Ltd., and China National Biotech Group
We previously found that a vaccine comprising a combination of four peptides from EV71 capsid protein (VP1–VP3) (Vac6, including P70–159, P140–249, P324–443, and P746–876 peptides) effectively elicited the production of neutralization antibodies in female mice and adequately protected neonatal mice against EV71 infection [28]

Summary

Introduction

Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. Foot, and mouth disease (HFMD) is extremely contagious and prevalent among infants and children aged less than 5 years. The latest large Asian epidemic was in mainland China during 2007 and 2008, with 488,955 cases as well as 126 deaths reported [10, 11]. Since the establishment of national surveillance system in 2008, more than 15 million HFMD cases were reported according to the China National Center for Disease Control (CDC) by 2015, with over 3400 deaths. All approved vaccines comprise inactivated viruses with the obvious advantage of almost complete immune protection; the vaccines are proved to protect over 90% vaccinated children from EV71-related HFMD or herpangina [10, 14, 15, 17]

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