Production of EV71 vaccine candidates.
Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective medications and/or prophylactic vaccines against HFMD are urgently needed. From a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of different EV71 vaccine candidates that have been produced and evaluated in animal models. Epitope-based synthetic peptide vaccine candidates containing residues 211-225 of VP1 formulated with Freund's adjuvant (CFA/IFA) elicited low EV71 virus neutralizing antibody responses, but were protective in the suckling mouse challenge model. Among recombinant EV71 subunits (rVP1, rVP2 and rVP3) expressed in E. coli, purified and formulated with CFA/IFA, only VP1 elicited mouse antibody responses with measurable EV71-specific virus neutralization titers. Immunization of mice with either a DNA plasmid containing VP1 gene or VP1 expressed in Salmonella typhimurium also generated neutralizing antibody responses and protected animals against a live EV71 challenge. Recombinant EV71 virus-like particles (rVLP) produced from baculovirus formulated either with CFA/IFA or alum elicited good virus neutralization titers in both mice and non-human primates, and were found to be protective in the suckling mouse EV71 challenge model. Synthetic peptides or recombinant EV71 subunit vaccines (rVP1 and rVLP) formulated in alum were found to be poorly immunogenic in rabbits. Only formalin-inactivated (FI) EV71 virions formulated in alum elicited cross-neutralizing antibodies against different EV71 genotypes in mice, rabbits and non-human primates but induced weak neutralizing responses against CAV16. From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials. We further describe and analyze some new bioprocesses technologies that have great potential applications in EV71 vaccine development. This review also demonstrates the opportunities and challenges that the Asian vaccine industry faces today.
['Chong|Pele|P|', 'Hsieh|Shih-Yang|SY|', 'Liu|Chia-Chyi|CC|', 'Chou|Ai-Hsiang|AH|', 'Chang|Jui-Yuan|JY|', 'Wu|Suh-Chin|SC|', 'Liu|Shih-Jen|SJ|', 'Chow|Yen-Hung|YH|', 'Su|Ih-Jen|IJ|', 'Klein|Michel|M|']
D000276:Adjuvants, Immunologic D000818:Animals D057134:Antibodies, Neutralizing D000914:Antibodies, Viral D000956:Antigens, Viral D002986:Clinical Trials as Topic D004195:Disease Models, Animal D029821:Enterovirus A, Human D005260:Female D006232:Hand, Foot and Mouth Disease D006801:Humans D008297:Male D051379:Mice D011323:Primates D011817:Rabbits D016019:Survival Analysis D015164:Vaccines, Inactivated D022223:Vaccines, Subunit D015678:Viral Structural Proteins D014765:Viral Vaccines
enterovirus 71 hand-foot-mouth diseases synthetic peptide virus neutralization titer virus-like particle formalin-inactivated whole virion vaccine