Comparative analysis of the immunogenicity and protective effects of inactivated EV71 vaccines in mice
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 b...
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| Published in: | PloS one Vol. 7; no. 9; p. e46043 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Public Library of Science
28-09-2012
Public Library of Science (PLoS) |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: Q Gao and WD Yin are affiliated to Sinovac Biotech Co., Ltd. ZB Guo is affiliated to Hualan Biological Engineering Inc.; XL Li and XL Shen are affiliated to National Vaccine and Serum Institute; CH Dong and QH Li are affiliated to Institute of Medical Biology, Chinese Academy of Medical Sciences. As a Board member, WD Yin holds shares of Sinovac Biotech Co., Ltd. There are EV71 vaccines in development to declare. There are no consultancies, patents, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies concerning sharing data and materials as detailed online in the guide for authors. Conceived and designed the experiments: ZL JW WY QL XS. Performed the experiments: CD XL QG ZG XY YW FG. Analyzed the data: QM FL MX. Contributed reagents/materials/analysis tools: ZL JW. Wrote the paper: QM ZL. |
| ISSN: | 1932-6203 1932-6203 |
| DOI: | 10.1371/journal.pone.0046043 |