COVID-19, the coronavirus disease of 2019, is one of the worst pandemics in human history. It emerged in December 2019 and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nearly 164 million SARS-CoV-2 infections and 3.4 million deaths have been reported globally since the beginning of the pandemic, which is still raging in many countries.
Efforts to mitigate the pandemic, which include masks, distancing from others, quarantines, contact tracking, and lockdowns, have only partially succeeded. Although there have been advances in finding treatment options to suppress SARS-CoV-2 replication or decrease the severity of the disease and mortality, prevention of disease using safe and effective SARS-CoV-2 vaccines is the ultimate solution to control this unprecedented pandemic. So far, 13 vaccines have been approved for emergency use in humans, and many such as the PTX-COVID19-B vaccine, are in different stages of clinical trials.
Considering the huge global numbers of people who need vaccination, the inequality in public health infrastructure in various countries, and the rapid emergence of new and more infectious SARS-CoV-2 variants with immune escape mechanisms, continued global effort is needed to stop this pandemic.
Evaluating the immunogenicity and safety of PTX-COVID19-B in mice and hamsters
Researchers from Canada recently reported the pre-clinical development of PTX-COVID19-B, a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine. PTX-COVID19-B has a full-length membrane-anchored S protein taken from the ancestral Wuhan-Hu-1 isolate with a D614G substitution to match the amino acid location of predominant SARS-CoV-2 strains in circulation currently.
The objective of their study was to evaluate the safety, immunogenicity, and efficacy of the vaccine in mice and hamsters. They chose PTX-COVID19-B from 3 candidate vaccines after the initial results showed that it elicited the most potent neutralizing antibody response against the SARS-CoV-2 virus in mice. The study is published on the preprint server, bioRxiv*.
Further tests in hamsters and mice indicated that PTX-COVID19-B induced strong cellular and humoral immune responses and offered complete protection to the vaccinated animals from SARS-CoV-2 infection in the lungs.
Experiments in hamsters revealed that PTX-COVID19-B protected the upper respiratory tract from infection. Suppression of viral replication in upper respiratory tracts reduces viral transmission to a large extent. However, this has been difficult to achieve with respiratory virus vaccines, which might be due to the poor ability of these vaccines to induce mucosal immunity in the upper respiratory tract. Some SARS-CoV-2 vaccines, including 1 of the 2 approved mRNA vaccines, were shown to have the ability to suppress the replication of the virus in both the upper and lower respiratory tract in animal studies.
Mouse immune sera elicited by the vaccine were able to neutralize variants of SARS-CoV-2, including the B.1.351, B.1.1.7, and P.1 lineages. No adverse effects were noticed in mice and hamsters vaccinated with PTX-COVID19-B.
PTX-COVID19-B is safe and effective in animals and is undergoing phase 1 clinical trials in humans
Based on the pre-clinical study results, Health Canada authorized this vaccine to enter clinical trials in December 2020. The phase 1 clinical trial for the vaccine is currently ongoing. Additional studies, such as the examination of the mucosal immune response induced by PTX-COVID19-B and tests to find out if PTX-COVID19-B can effectively prevent transmission among hamsters, are needed to confirm the upper respiratory tract findings reported in this study.
To summarize, PTX-COVID19-B is a is highly immunogenic and safe mRNA vaccine that prevents SARS-CoV-2 infection in hamsters and mice and is currently being evaluated in a phase 1 human clinical trial. This trial will determine if PTX-COVID19-B is eligible to enter the subsequent phases of clinical trials and eventually gets approved for use in humans to strengthen the global fight against the COVID-19 pandemic.
“Although a few vaccines have been approved for emergency use in humans, additional safe, effective, and easily deployable SARS-CoV-2 vaccines are needed to meet the enormous challenge for the global immunization required to end the COVID-19 pandemic.”
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B Jun Liu, Patrick Budylowski, Reuben Samson, Bryan D. Griffin, Giorgi Babuadze, Bhavisha Rathod, Karen Colwill, Jumai A. Abioye, Jordan A Schwartz, Ryan Law, Lily Yip, Sang Kyun Ahn, Serena Chau, Maedeh Naghibosadat, Yuko Arita, Queenie Hu, Feng Yun Yue, Arinjay Banerjee, Karen Mossman, Samira Mubareka, Robert A. Kozak, Michael S. Pollanen, Natalia Martin Orozco, Anne-Claude Gingras, Eric G. Marcusson, Mario A. Ostrowski, bioRxiv, 2021.05.11.443286; doi: https://doi.org/10.1101/2021.05.11.443286, https://www.biorxiv.org/content/10.1101/2021.05.11.443286v1