Abstract
Enterovirus 71 (EV71) is a major etiological agent of various public health issues, particularly in the Asia-Pacific region. EV71 causes hand-foot-and-mouth disease (HFMD) and is associated with serious neurological disorders in young children. A formalin-inactivated EV71 candidate vaccine (KCDC-HFMDV1-EV71) based on the C4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of EV71 infection in mice. In this study, an inactivated EV71 vaccine was used for analysis of long-term immunogenicity and efficacy in cynomolgus monkeys, a common nonhuman primate model. The vaccine was immunized three times at 0, 4, and 8 weeks with either 20-μg doses of EV71 candidate vaccine formulated with aluminum hydroxide gel adjuvant or phosphate-buffered saline as a control. The group immunized with the inactivated EV71 showed significantly increased EV71-specific antibody and serum neutralizing antibody titers at 3 weeks after vaccination and maintained these elevated titers until the end of the experiment (54 weeks after vaccination). The sera from vaccinated cynomolgus monkeys showed a crossreactive neutralizing antibody response to the heterologous subtype of EV71 (B1–4, C1, and C2). These findings suggest that the inactivated EV71 candidate vaccine may be a potential vaccine candidate and valuable tool for the control of HFMD.
Highlights
Enterovirus 71 (EV71) infection has emerged as a serious threat to public health in young children worldwide [1]
These results indicated that the inactivated EV71 vaccine used in this study was safe
Various approaches, including live-attenuated virus vaccines, inactivated virus vaccines using cell culture systems, virus-like particle (VLP) vaccines expressed by baculovirus systems in insect cells, subunit vaccines, have been used to develop an ideal EV71 vaccine to prevent hand-foot-and-mouth disease (HFMD) [14,15,16,17,18,19,20]
Summary
Enterovirus 71 (EV71) infection has emerged as a serious threat to public health in young children worldwide [1]. EV71 belongs to the genus Enterovirus, family Picornaviridae. EV71 is a nonenveloped, single-stranded, positive-sense RNA virus and is classified into four genotypes, i.e., genotypes A, B, C, and D, based on the VP1 gene sequence. Genotypes A and D are represented by single strains, i.e., BrCr and India strains, respectively, whereas genotypes B and C. Enterovirus 71 inactivated vaccine in cynomolgus monkey were each divided five subgenotypes, designated B1–B5 and C1–C5. Genotypes B and C are distributed worldwide, whereas genotype A is much less common [2, 3]. Recombination events between genotypes of EV71 have generated a new subgenotype [4]
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