Academic Journal
Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against DENV-2 and -4
| العنوان: | Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against DENV-2 and -4 |
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| المؤلفون: | Barban, Veronique, Mantel, Nathalie, De Montfort, Aymeric, Pagnon, Anke, Pradezynski, Fabrine, Lang, Jean, Boudet, Florence |
| المساهمون: | Diamond, Michael S. |
| المصدر: | Journal of Virology ; volume 92, issue 12 ; ISSN 0022-538X 1098-5514 |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2018 |
| الوصف: | Recent data obtained with the live-attenuated tetravalent dengue CYD-TDV vaccine showed higher protective efficacy against dengue virus type 4 (DENV-4) than against DENV-2. In contrast, results from previous studies in nonhuman primates predicted comparable high levels of protection against each serotype. Maximum viral loads achieved in macaques by subcutaneous inoculation of DENV are generally much lower than those observed in naturally dengue virus-infected humans. This may contribute to an overestimation of vaccine efficacy. Using more-stringent DENV infection conditions consisting of the intravenous inoculation of 10 7 50% cell culture infectious doses (CCID 50 ) in CYD-TDV-vaccinated macaques, complete protection (i.e., undetectable viral RNA) was achieved in all 6 monkeys challenged with DENV-4 and in 6/18 of those challenged with DENV-2, including transiently positive animals. All other infected macaques (12/18) developed sustained DENV-2 RNAemia (defined as detection of viral RNA in serum samples) although 1 to 3 log 10 units below the levels achieved in control animals. Similar results were obtained with macaques immunized with either CYD-TDV or monovalent (MV) CYD-2. This suggests that partial protection against DENV-2 was mediated mainly by CYD-2 and not by the other CYDs. Postchallenge induction of strong anamnestic responses, suggesting efficient vaccine priming, likely contributed to the reduction of DENV-2 RNAemia. Finally, an inverse correlation between DENV RNA titers postchallenge and vaccine-induced homotypic neutralizing antibody titers prechallenge was found, emphasizing the key role of these antibodies in controlling DENV infection. Collectively, these data show better agreement with reported data on CYD-TDV clinical vaccine efficacy against DENV-2 and DENV-4. Despite inherent limitations of the nonhuman primate model, these results reinforce its value in assessing the efficacy of dengue vaccines. IMPORTANCE The nonhuman primate (NHP) model is the most widely recognized tool for ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1128/jvi.00440-18 |
| DOI: | 10.1128/JVI.00440-18 |
| الاتاحة: | http://dx.doi.org/10.1128/jvi.00440-18 https://journals.asm.org/doi/pdf/10.1128/JVI.00440-18 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ ; https://journals.asm.org/non-commercial-tdm-license |
| رقم الانضمام: | edsbas.51159F4A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/jvi.00440-18 |
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