Comparative Analysis of the Immunogenicity and Protective Effects of Inactivated EV71 Vaccines in Mice |
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Authors: | 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 |
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Institution: | 1. National Institutes for Food and Drug Control, Beijing, China.; 2. Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, China.; 3. National Vaccine and Serum Institute, Beijing, China.; 4. Sinovac Biotech Co., Ltd., Beijing, China.; 5. Hualan Biological Engineering Inc, Henan, China.; University of Illinois at Chicago, United States of America, |
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Abstract: | BackgroundEnterovirus 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.Methods and FindingsThis 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 LD50 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 ED50 of NAb responses and protective effects varied among three FCP-As.ConclusionsThese 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. |
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