دورية أكاديمية

Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.

التفاصيل البيبلوغرافية
العنوان: Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.
المؤلفون: Darci R Smith, Sara C Johnston, Ashley Piper, Miriam Botto, Ginger Donnelly, Joshua Shamblin, César G Albariño, Lisa E Hensley, Connie Schmaljohn, Stuart T Nichol, Brian H Bird
المصدر: PLoS Neglected Tropical Diseases, Vol 12, Iss 5, p e0006474 (2018)
بيانات النشر: Public Library of Science (PLoS), 2018.
سنة النشر: 2018
المجموعة: LCC:Arctic medicine. Tropical medicine
LCC:Public aspects of medicine
مصطلحات موضوعية: Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
الوصف: Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1935-2727
1935-2735
Relation: http://europepmc.org/articles/PMC5962102?pdf=render; https://doaj.org/toc/1935-2727; https://doaj.org/toc/1935-2735
DOI: 10.1371/journal.pntd.0006474
URL الوصول: https://doaj.org/article/203ffc5bf0474aa19283043192efcc6e
رقم الأكسشن: edsdoj.203ffc5bf0474aa19283043192efcc6e
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19352727
19352735
DOI:10.1371/journal.pntd.0006474