PLoS ONE (Jan 2012)

Comparative analysis of the immunogenicity and protective effects of inactivated EV71 vaccines in mice.

  • Qunying Mao,
  • Chenghong Dong,
  • Xiuling Li,
  • Qiang Gao,
  • Zengbing Guo,
  • Xin Yao,
  • Yiping Wang,
  • Fan Gao,
  • Fengxiang Li,
  • Miao Xu,
  • Weidong Yin,
  • Qihan Li,
  • Xinliang Shen,
  • Zhenglun Liang,
  • Junzhi Wang

DOI
https://doi.org/10.1371/journal.pone.0046043
Journal volume & issue
Vol. 7, no. 9
p. e46043

Abstract

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Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD). Three inactivated EV71 whole-virus vaccines of different strains developed by different manufacturers in mainland China have recently entered clinical trials. Although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. Thus, properly comparing newly developed vaccines has become a priority, especially in China.This comparative immunogenicity study was carried out on vaccine strains (both live and inactivated), final container products (FCPs) without adjuvant, and corresponding FCPs containing adjuvant (FCP-As) produced by three manufacturers. These vaccines were evaluated by neutralizing antibody (NAb) responses induced by the same or different dosages at one or multiple time points post-immunization. The protective efficacy of the three vaccines was also determined in one-day-old ICR mice born to immunized female mice. Survival rates were observed in these suckling mice after challenge with 20 LD(50) of EV71/048M3C2. Three FCP-As, in a dose of 200 U, generated nearly 100% NAb positivity rates and similar geometric mean titers (GMTs), especially at 14-21 days post-inoculation. However, the dynamic NAb responses were different among three vaccine strains or three FCPs. The FCP-As at the lowest dose used in clinical trials (162 U) showed good protective effects in suckling mice against lethal challenge (90-100% survival), while the ED(50) of NAb responses and protective effects varied among three FCP-As.These studies establish a standard method for measuring the immunogenicity of EV71 vaccines in mice. The data generated from our mouse model study indicated a clear dose-response relationship, which is important for vaccine quality control and assessment, especially for predicting protective efficacy in humans when combined with future clinical trial results.