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A virus-like particle-based tetravalent vaccine for hand, foot, and mouth disease elicits broad and balanced protective immunity.


ABSTRACT: Hand, foot, and mouth disease (HFMD) is an infectious disease that mainly affects infants and children, causing considerable morbidity and mortality worldwide. HFMD is commonly caused by enterovirus 71 (EV71) and coxsackieviruses A16 (CVA16), A6 (CVA6), and A10 (CVA10). Formalin-inactivated EV71 vaccines are currently available in China; however, these vaccines fail to confer cross-protection against infections by other HFMD-causing enteroviruses, highlighting the necessity of developing a multivalent HFMD vaccine. Our previous studies demonstrated that recombinant virus-like particles (VLP) of EV71, CVA16, and CVA6 are capable of inducing protective immunity against homologous virus challenges in mice. In this study, we generated CVA10-VLP using a baculovirus-insect cell expression system and then combined CVA10-VLP with EV71-VLP, CVA16-VLP, and CVA6-VLP to formulate a tetravalent VLP vaccine. Immunogenicity and protective efficacy of tetravalent VLP vaccine was compared with that of monovalent VLP vaccines. Mouse immunization studies revealed that the tetravalent vaccine elicited antigen-specific and long-lasting serum antibody responses comparable to those elicited by its corresponding monovalent vaccines. Moreover, tetravalent vaccine immune sera strongly neutralized EV71, CVA16, CVA10, and CVA6 strains with neutralization titers similar to those of their monovalent counterparts, indicating a good compatibility among the four antigens in the combination vaccine. Importantly, passively transferred tetravalent vaccine-immunized sera conferred efficient protection against single or mixed infections with EV71, CVA16, CVA10, and CVA6 viruses in mice, whereas the monovalent vaccines could only protect mice against homotypic virus infections but not heterotypic challenges. These results demonstrate that the tetravalent VLP vaccine represents a promising broad-spectrum HFMD vaccine candidate.

SUBMITTER: Zhang W 

PROVIDER: S-EPMC5959873 | BioStudies | 2018-01-01

SECONDARY ACCESSION(S): 10.7774/cevr.2017.6.1.4

REPOSITORIES: biostudies

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Enterovirus 71 infection and vaccines.

Yi Eun-Je EJ   Shin Yun-Ju YJ   Kim Jeong-Hwan JH   Kim Tae-Gyun TG   Chang Sun-Young SY  

Clinical and experimental vaccine research 20170125 1


Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting young children during the spring to fall seasons. Recently, serious outbreaks of HFMD were reported frequently in the Asia-Pacific region, including China and Korea. The symptoms of HFMD are usually mild, comprising fever, loss of appetite, and a rash with blisters, which do not need specific treatment. However, there are uncommon neurological or cardiac complications such as meningitis and acute flaccid paralys  ...[more]

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