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Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice | ||
Iranian Journal of Medical Sciences | ||
مقاله 5، دوره 42، شماره 2، خرداد 2017، صفحه 152-160 اصل مقاله (715.41 K) | ||
نوع مقاله: Original Article(s) | ||
نویسندگان | ||
Ajit Kulkarni* 1؛ Rushil Bhat1؛ Mansi Malik2؛ Suvarna Sane3؛ Sweta Kothari1؛ Shashikant Vaidya1؛ Abhay Chowdhary1؛ Ranjana A Deshmukh1 | ||
1Department of Virology, Haffkine Institute for Traning, Research and Testing, Acharya Donde Marg, Mumbai-400012 India | ||
2Department of Zoonosis, Haffkine Institute for Traning, Research and Testing, Acharya Donde Marg, Mumbai-400012 India | ||
3National AIDS Research Institute, MIDC, Bhosari, Pune-411026 India | ||
چکیده | ||
Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group) each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid) (100µg, i.m.) on days 0, 14 and 28. Among these, four groups (one group per serotype) of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV) serotypes 1-4 (100 LD50, 20 µl intracerebrally) to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively.Results: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4) and 50% (DENV-2).Conclusion: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2. | ||
کلیدواژهها | ||
Dengue؛ Envelope domain III (EDIII)؛ Antibodies؛ Neutralizing؛ Vaccines | ||
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