Abstract
Enterovirus 71 (EV71) is the most frequently detected causative agent in hand, foot, and mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. Many EV71 vaccines are under development worldwide, and although both inactivated virus vaccines and virus-like particles (VLPs) are considered to be effective, the main focus has been on inactivated EV71vaccines. There have been very few studies on EV71 VLPs. In this study, using a strategy based on HIV gag VLPs, we constructed a gag-VP1 fusion gene to generate a recombinant baculovirus expressing the EV71 structural protein VP1 together with gag, which was then used to infect TN5 cells to form VLPs. The VLPs were characterized using transmission electron microscopy, electrophoresis and staining with Coomassie blue, and Western blotting. Mice immunized with gag-VP1 VLPs showed strong humoral and cellular immune responses. Finally, immunization of female mice with gag-VP1 VLPs provided effective protection of their newborn offspring against challenge with a lethal dose EV71. These results demonstrate a successful approach for producing EV71 VP1 VLPs based on the ability of HIV gag to self-assemble, thus providing a good foundation for producing high-titered anti-EV71 antibody by immunization with VLP-based gag EV71 VP1 protein.
Highlights
Human enterovirus 71 (EV71) is a non-enveloped RNA virus belonging to the family Picornaviridae that was first reported and isolated in the year 1969 [1, 2]
Many Enterovirus 71 (EV71) vaccines are under development worldwide, and both inactivated virus vaccines and virus-like particles (VLPs) are considered to be effective, the main focus has been on inactivated EV71vaccines
One-day-old newborn mice (6 mice per group) were inoculated intraperitoneally (i.p.) with sera from mice immunized with gag-VP1 VLPs, inactivated EV71 virus or phosphate-buffered saline (PBS)
Summary
Human enterovirus 71 (EV71) is a non-enveloped RNA virus belonging to the family Picornaviridae that was first reported and isolated in the year 1969 [1, 2]. It has been identified as one of the major causative agents of hand, foot, and mouth disease (HFMD), which mostly affects children under the age of six [2, 3]. During the last 10 years, large-scale outbreaks of HFMD have been reported with increasing prevalence in China [8, 9]. Vaccination is one of the most effective strategies for preventing and reducing the prevalence of viral infectious diseases, including HFMD, and many approaches have been tested in order to develop safe and efficient EV71 vaccines [10]
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