A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike
| العنوان: | A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike |
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| المؤلفون: | Jianming Qiu, Xueya Liang, Octavio Ramilo, Chuanxi Cai, Luis Martinez-Sobrido, Chengjin Ye, Ashley Zani, Stefan Niewiesk, Masako Shimamura, Sheetal Trivedi, Prosper N. Boyaka, Piyush Dravid, Adam D. Kenney, Jacob S. Yount, Jianrong Li, Mahesh Kc, Shan-Lu Liu, Amit Kapoor, Supranee Chaiwatpongsakorn, Anzhong Li, Asuncion Mejias, Mijia Lu, Cong Zeng, Olivia Harder, Mark E. Peeples, Yuexiu Zhang |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, viruses, Gene Expression, Antibodies, Viral, law.invention, Mice, Immunogenicity, Vaccine, 0302 clinical medicine, law, Cricetinae, SARS-CoV-2 vaccine, 030212 general & internal medicine, Neutralizing antibody, Vaccines, Synthetic, Multidisciplinary, Attenuated vaccine, biology, Biological Sciences, Spike Glycoprotein, Coronavirus, Recombinant DNA, Antibody, measles virus vector, COVID-19 Vaccines, Genetic Vectors, Mice, Transgenic, Microbiology, Measles virus, prefusion spike, 03 medical and health sciences, medicine, Animals, Humans, Cotton rat, business.industry, COVID-19, biology.organism_classification, medicine.disease, Antibodies, Neutralizing, Virology, Rats, Disease Models, Animal, 030104 developmental biology, Immunization, biology.protein, Cytokine storm, business |
| الوصف: | Significance Measles virus (MeV) vaccine is one of the safest and most efficient vaccines with a track record in children. Here, we generated a panel of rMeV-based vaccines with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S antigens inserted near 3′ of the MeV genome. The rMeV expressing a soluble stabilized, prefusion spike (preS) is much more potent in triggering SARS-CoV-2–specific neutralizing antibody than rMeV-based full-length S vaccine candidate. A single dose of rMeV-preS is sufficient to induce high levels of SARS-CoV-2 antibody in animals. Furthermore, rMeV-preS induces high levels of Th1-biased immunity. Hamsters immunized with rMeV-preS were completely protected against SARS-CoV-2 challenge. Our results demonstrate rMeV-preS is a safe and highly efficacious bivalent vaccine candidate for SARS-CoV-2 and MeV. The current pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR−/−mice, IFNAR−/−-hCD46 mice, and golden Syrian hamsters. We found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2–specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent. Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response. The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, body weight loss, cytokine storm, and lung pathology. These data demonstrate that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2026153118 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d7285a8787354e07217eea79c31df0d https://doi.org/10.1073/pnas.2026153118 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7d7285a8787354e07217eea79c31df0d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.2026153118 |