Colorized scanning electron micrograph of a VERO E6 cell (blue) heavily infected with SARS-COV-2 virus particles (orange), isolated from a patient sample. Image captured and color enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Vaccine shows promise in mouse studies and is currently being evaluated in Phase 3 clinical trials.
The research vaccine known as mRNA-1273 protects mice against infection with SARS-CoV-2, the virus that causes it COVID-19, according to research published today in Nature. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the biotechnology company Moderna, based in Cambridge, Massachusetts, together with collaborators from the University of North Carolina at Chapel Hill, Vanderbilt University Medical Center in Nashville, and the University of Texas at Austin conducted preclinical research. Scientists from NIAID Vaccine Research (VRC) collaborated with researchers from the University of Texas at Austin to identify the atomic structure of the spike protein on the surface of the new coronavirus. This structure was used by VRC and Moderna in the development of the vaccine candidate.
The findings show that the research vaccine induced neutralizing antibodies in mice when given as two intramuscular injections at a dose of 1 microgram (mcg) with three weeks apart. Additional experiments found that mice received two injections of the 1-mcg dose and were later challenged with SARS-CoV-2 virus, whether 5 or 13 weeks after the second injection were protected against viral replication in the lungs and nose. Importantly, mice challenged 7 weeks after only a single dose of 1 mcg or 10 mcg of mRNA-1273 were also protected against viral replication in the lung..
The research vaccine also elicited robust CD8 T cell responses in mice. It does not induce the type of cellular immune response associated with vaccine-associated enhanced respiratory disease (VAERD). This rare, allergic type of inflammation was seen in individuals who were vaccinated with a highly inactivated respiratory syncytial virus (RSV) vaccine in the 1960s. VAERD can occur if a vaccine induces an immune response that is not strong enough to protect against infection. The researchers foxed mice with sub-protective doses of mRNA-1273 and then challenged the mice with SARS-CoV-2. The mice showed no evidence of improved lung pathology or excessive muscle production, indicating that the vaccine did not cause improved disease, the authors write.
The authors note that the data from these studies, combined with data from studies in nonhuman primates and Phase 1 clinical trials, support the evaluation of mRNA-1273 in clinical efficacy tests. They also explain how their preliminary investigation into a candidate MERS-CoV vaccine paved the way for a rapid response to the COVID-19 outbreak. “This is a demonstration of how the power of new technology-driven concepts such as synthetic vaccinology facilitates a vaccine development program that can be initiated with pathogen sequences only,” the authors write.
Reference: “SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparation” by Kizzmekia S. Corbett, Darin K. Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J. Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kai Wu, Carole Henry, Kapil Bahi, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Emily Phung, Lauren A Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Cuiping Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L. Gully, Laura J Stevens , Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Gabriela S. Alvarado, Martha C. Nason, Tracy J. Ruckward t, Jacket on S. McLellan, Mark R. Denison, James D. Chappell, Ian N. Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi and Barney S. Graham, 5 August 2020, Nature.
DOI: 10.1038 / s41586-020-2622-0
