Protective effect of enterovirus‑71 (EV71) virus‑like particle vaccine against lethal EV71 infection in a neonatal mouse model.
Enterovirus-71 (EV71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (HFMD) among young children, with significant mortality. Effective vaccines against HFMD are urgently required. Several EV71 virus-like particle (VLP) vaccine candidates were found to be protective in the neonatal mouse EV71 challenge model. However, to what extent the VLP vaccine protects susceptible organs against EV71 infection in vivo has remained elusive. In the present study, the comprehensive immunogenicity of a potential EV71 vaccine candidate based on VLPs was evaluated in a neonatal mouse model. Despite lower levels of neutralizing antibodies to EV71 in the sera of VLP-immunized mice compared with those in mice vaccinated with inactivated EV71, the VLP-based vaccine was shown to be able to induce immunoglobulin (Ig)G and IgA memory-associated cellular immune responses to EV71. Of note, the EV71 VLP vaccine candidate was capable of inhibiting viral proliferation in cardiac muscle, skeletal muscle, lung and intestine of immunized mice and provided effective protection against the pathological damage caused by viral attack. In particular, the VLP vaccine was able to inhibit the transportation of EV71 from the central nervous system to the muscle tissue and greatly protected muscle tissue from infection, along with recovery from the viral infection. This led to nearly 100% immunoprotective efficacy, enabling neonatal mice delivered by VLP-immunized female adult mice to survive and grow with good health. The present study provided valuable additional knowledge of the specific protective efficacy of the EV71 VLP vaccine in vivo, which also indicated that it is a promising potential candidate for being developed into an EV71 vaccine.
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Lei
L
Cao
Laboratory Animal Center, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Fengfeng
F
Mao
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Zheng
Z
Pang
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Yao
Y
Yi
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Feng
F
Qiu
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Ruiguang
R
Tian
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Qingling
Q
Meng
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Zhiyuan
Z
Jia
Department of Viral Hepatitis, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing 102206, P.R. China.
Shengli
S
Bi
D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000821:virology; D009206:Myocardium / Q000276:immunology; D009500:Neutralization Tests; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines