Induction of a high-titered antibody response using HIV gag-EV71 VP1-based virus-like particles with the capacity to protect newborn mice challenged with a lethal dose of enterovirus 71

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.