tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Mar 23;118(12):e2026153118.
doi: 10.1073/pnas.2026153118.
A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike
Mijia Lu[SUP] 1 [/SUP], Piyush Dravid[SUP] 2 [/SUP], Yuexiu Zhang[SUP] 1 [/SUP], Sheetal Trivedi[SUP] 2 [/SUP], Anzhong Li[SUP] 1 [/SUP], Olivia Harder[SUP] 1 [/SUP], Mahesh Kc[SUP] 2 [/SUP], Supranee Chaiwatpongsakorn[SUP] 2 [/SUP], Ashley Zani[SUP] 3 [/SUP], Adam Kenney[SUP] 3 [/SUP], Cong Zeng[SUP] 1 [/SUP], Chuanxi Cai[SUP] 4 [/SUP], Chengjin Ye[SUP] 5 [/SUP], Xueya Liang[SUP] 1 [/SUP], Masako Shimamura[SUP] 2 6 [/SUP], Shan-Lu Liu[SUP] 1 3 7 8 [/SUP], Asuncion Mejias[SUP] 2 6 [/SUP], Octavio Ramilo[SUP] 2 6 [/SUP], Prosper N Boyaka[SUP] 1 7 [/SUP], Jianming Qiu[SUP] 9 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP], Jacob S Yount[SUP] 3 7 [/SUP], Mark E Peeples[SUP] 2 6 7 [/SUP], Amit Kapoor[SUP] 2 6 7 [/SUP], Stefan Niewiesk[SUP] 1 7 [/SUP], Jianrong Li[SUP] 10 7 [/SUP]
Affiliations
Abstract
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[SUP]-/-[/SUP]mice, IFNAR[SUP]-/-[/SUP]-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.
Keywords: SARS-CoV-2 vaccine; measles virus vector; prefusion spike.
. 2021 Mar 23;118(12):e2026153118.
doi: 10.1073/pnas.2026153118.
A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike
Mijia Lu[SUP] 1 [/SUP], Piyush Dravid[SUP] 2 [/SUP], Yuexiu Zhang[SUP] 1 [/SUP], Sheetal Trivedi[SUP] 2 [/SUP], Anzhong Li[SUP] 1 [/SUP], Olivia Harder[SUP] 1 [/SUP], Mahesh Kc[SUP] 2 [/SUP], Supranee Chaiwatpongsakorn[SUP] 2 [/SUP], Ashley Zani[SUP] 3 [/SUP], Adam Kenney[SUP] 3 [/SUP], Cong Zeng[SUP] 1 [/SUP], Chuanxi Cai[SUP] 4 [/SUP], Chengjin Ye[SUP] 5 [/SUP], Xueya Liang[SUP] 1 [/SUP], Masako Shimamura[SUP] 2 6 [/SUP], Shan-Lu Liu[SUP] 1 3 7 8 [/SUP], Asuncion Mejias[SUP] 2 6 [/SUP], Octavio Ramilo[SUP] 2 6 [/SUP], Prosper N Boyaka[SUP] 1 7 [/SUP], Jianming Qiu[SUP] 9 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP], Jacob S Yount[SUP] 3 7 [/SUP], Mark E Peeples[SUP] 2 6 7 [/SUP], Amit Kapoor[SUP] 2 6 7 [/SUP], Stefan Niewiesk[SUP] 1 7 [/SUP], Jianrong Li[SUP] 10 7 [/SUP]
Affiliations
- PMID: 33688034
- DOI: 10.1073/pnas.2026153118
Abstract
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[SUP]-/-[/SUP]mice, IFNAR[SUP]-/-[/SUP]-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.
Keywords: SARS-CoV-2 vaccine; measles virus vector; prefusion spike.