mRNA Vaccines

Katalin Kariko and Drew Weissman are the recipients of the 2023 Nobel Prize in Physiology or Medicine. While mRNA medicines had been researched for years, they could not be used at the time because synthetic mRNA often caused dangerous immune reactions from the body, similar to the reaction catalyzed by contact with a virus. By replacing the RNA building block “uridine” with a modified version called “pseudouridine,” they avoided triggering an immune response. This change also made mRNA more stable and improved its ability to produce proteins inside cells. Their work solved core issues that had kept mRNA technology from being implemented in healthcare.

Because of their discoveries, vaccine development changed rapidly. Kariko and Weissman’s methods allowed for the streamlined design of vaccines that only required the genome of the virus they are targeting. Notably, this technique was then used to create the Pfizer and Moderna COVID-19 vaccines. Even before the pandemic, their research had already inspired new directions in treating diseases through vaccines and protein therapy. These breakthroughs have made the overall process of vaccine research and development faster and more effective overall.

MERS-CoV and SARS-CoV-2 are members of the betacoronavirus family that both use the (S) spike protein to enter host cells. If these spike proteins can somehow be damaged or rendered useless, then the viral particles will be unable to create an infection. For these reasons, researchers were aiming to create a vaccine to neutralize the viral spikes. According to this article, prior research on MERS-CoV allowed scientists to understand how to stabilize the spike protein in its prefusion shape, which is what triggers an immune response. There is a “2P” mutation that naturally presents itself in MERS-CoV that stabilizes the spike protein. This mutation was transplanted onto the SARS-CoV-2 spike, rendering the same effect as in its original organism. The researchers were then able to adapt the mRNA platform for COVID-19 once the new viral sequence was isolated.

Vaccine trials also guided the safety and dosing strategies used for COVID-19 vaccines. The article mentioned above reported that vaccine experiments using lipid nanoparticles (LNPs) demonstrated that mRNA vaccines could provide strong immune protection without severe side effects. These findings gave researchers confidence that mRNA was a safe and effective platform for coronavirus vaccines. The same study also shows how “prototype pathogen” preparedness allowed researchers to move through phases of experimentation and clinical trials at an unheard-of pace. This article suggests that the combination of prior MERS research, validated vaccine designs, and pandemic planning directly enabled the rapid and successful creation of COVID-19 mRNA vaccines.

Israeli research consisting of a large, nationwide health-care database to compare vaccinated individuals with matched unvaccinated controls. Their study found that vaccinated people had significantly lower risks of infection, hospitalization, and COVID-19–related death than those who did not get vaccinated. Because COVID-19 was a leading cause of excess mortality at the time, it was concluded that vaccination reduced both COVID-specific and overall mortality in the population studied. Reports indicated a small increased risk of myocarditis after vaccination, estimated to be somewhere between 1 and 5 cases per 100,000 vaccinees in the short period following vaccination. This data validates the claim that myocarditis is one of the adverse events associated with the vaccine. The study also notes that for males between the ages of 16 and 30, the prevalence may be closer to about 10 cases per 100,000.

These researchers compared the small excess risk of myocarditis after vaccination with the much higher risks of serious outcomes, including myocarditis, following SARS-CoV-2 infection. They concluded that the overall safety profile of the “BNT162b2” vaccine was favorable and that its benefits in preventing infection, hospitalization, and COVID-19 death outweighed the relatively rare risk of myocarditis. Most post-vaccine myocarditis cases were mild and resolved with standard care. The study emphasizes the importance of continued monitoring and clinical management of myocarditis as a rare adverse event. Overall, the authors support vaccination while acknowledging the need for vigilance regarding uncommon cardiac complications.