Since the infection of enterovirus 71 / EV71 primarily affects countries in the Asia-Pacific region, there is little incentive for vaccine companies from developed countries to develop enterovirus 71 / EV71 vaccines, and mainly the companies and institutes in Asia make efforts to take the vaccines from research to product launch. The ideal candidates for enterovirus 71 / EV71 vaccine should elicit strong cross-genotype neutralizing antibody response and have low costs of the finished products. Candidates based on synthetic peptides, recombinant subunits, virus-like particles, and chemically-inactivated virions are in consideration.
Due to their intrinsically poor immunogenic ability, neutralization epitopes-based enterovirus 71 / EV71 vaccines should be formulated in strong adjuvant such as CFA, which are not approved by FDA right now. Similar situation has been met by recombinant subunit-based enterovirus 71 / EV71 vaccine candidates. For the VLP-based EV71 vaccine candidate, neutralizing antibody responses will be induced only when high dose of them are formulated with alum; there also should be a long time for the construction of recombinant baculovirus VLP-EV71 and the GMP certification of the insect cells; in addition, the high cost of production will be an obstacle for VLP-EV71 vaccine development.
A stable and cost-effective enterovirus 71 / EV71 may be developed based on formalin-inactivated virions that can induce cross-genotype neutralizing antibody responses in mice and non-human primate models. Five inactivated enterovirus 71 / EV71 virion vaccines have been produced in China, Taiwan and Singapore, and have entered into phase 1 or 2 human clinical trials.
|Manufacturing processes||Clinical trials||Reference (clinicaltrials. Gov Identifier)|
|Organizations||Cell lines and EV71 strain||UP-stream||Down-stream||Dosage (μg of EV71 antigen)||Population target||Current status|
|NHRIa (Taiwan)||Vero cell and EV71 B4 subgenotype (GMP-certified)||Roller-bottle (Serum-free media)||Gel-filtration Chromatography||5 and 10||Young adults||Phase 1 completed||NCT01268787|
|Sinovac (China)||Vero cell and EV71 C4 subgenotype||Cell factory (Serum-free media)||Gel-filtration Chromatography||0.25, 0.5 and 1||Young adults, young children and infants||Phase 1 and 2 completed Phase 3 now||NCT01273246, NCT01273233, NCT01507857|
|Beijing Vigoo (China)||Vero cell and EV71 C4 subgenotype||Cell factory (Serum-free media)||Gel-filtration Chromatography||0.4, 0.8 and 1.6||Young adults, young children and infants||Phase 1 and 2 completed Phase 3 now||NCT01313715, NCT01399853, NCT01508247|
|CAMS (China)||Human diploid cell KMB-17 and EV71 C4 subgenotype||Cell factory (Serum-free media)||Gel-filtration Chromatography||Unknown||Young adults, young children and infants||Phase 1 and 2 completed Phase 2 now||NCT01391494, NCT01512706|
|Inviragen (Singapore)||Vero cell and EV71 B3 subgenotype||Cell factory (Serum-free media)||Gel-filtration Chromatography||0.3 and 3||Young adults||Phase 1 completed||NCT01376479|
Table 2. Formalin-inactivated EV71 whole-virus vaccine candidates currently being tested in clinical trials
|Malaysia||C1, C2, B3, B4||C1||C1||B4, C1||C1||B5, C1||B5, C1||B5|
|Singapore||B3, B4||B3, C1||B3||B4||B4||B4, C1||B5||B5|
|Taiwan||B4, C2, C4||B4||B4||B4||B4, C4||B4, B5||C4||C4||C5||B5, C5||B5||B5||C4|
|Japan||C2, B3, B4||C2||C2||C2, B4||C2||B4, C2, C4||C4, B5||C4||C4||C4|
|Vietnam||C1, C4, C5|
|Australia||C2||B3, C2||B4, C1||B4, C1||C1||C1||C4|
|The Netherlands||C1, C2||C2||C2||C1||C1, C2||C1, C2||C1, C2||C1, C2||C2|
|United Kingdom||C1||C1, C2||C1||C1||C1||C1||C1, C2|
Bold indicates predominant genotype.
Table 1. Distribution of EV71 genotypes throughout the world from 1997 to 2010
|What is Enterovirus 71 (EV71)?||Biological Characteristics of Enterovirus 71 (EV71)|
|Genetic Variations of Enterovirus 71 (EV71)||Clinical Development of Enterovirus 71 (EV71) Vaccine|
|Potential Drug Targets of Enterovirus 71 (EV71)|