title: Vesicular stomatitis virus-based vaccines expressing EV71 virus-like particles elicit strong immune responses and protect newborn mice from lethal challenges.
abstract: Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered 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. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLPs. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Linjuan
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Longyun
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: yqin@whu.edu.cn.
authors.forename: Yali
authors.initials: Y
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: zspan@whu.edu.cn.
authors.forename: Zishu
authors.initials: Z
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: chenmz@whu.edu.cn.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D029821:Enterovirus A, Human; D004769:Enterovirus Infections / Q000517:prevention & control; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D016207:Cytokines; C442501:VP1 protein, Foot-and-mouth disease virus; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines
keywords: EV71 virus-like particles; Vesicular stomatitis virus