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Providence Therapeutics Publishes two New Papers Highlighting the Potential of mRNA Vaccines to Outpace Evolving Viruses Like COVID-19

CALGARY, Alberta, January 13, 2025 – Are we forced to keep updating vaccines to chase fast-changing viruses such as COVID-19 and flu viruses? Two newly published papers from the scientists at Providence Therapeutics Holdings, Inc. (PT) and their collaborators show that we may outsmart the viruses, by using mRNA vaccines.

In the first paper that was published in npj Vaccines, https://rdcu.be/d5NGx, a bivalent mRNA vaccine made by PT was found to induce broadly reactive immune responses against multiple COVID-19 virus strains, including the recently circulating ones, such as Omicron XBB.1.5 and JN.1, even though they were not included in the bivalent mRNA vaccine (The bivalent mRNA vaccine encodes the two spike proteins, one from the original COVID-19 virus and one from an old Omicron strain). Furthermore, the bivalent mRNA vaccines can protect mice and hamsters from infection by multiple strains of COVID-19 virus, including XBB.1.5. The underlying mechanisms for this broad protection are the potent antibodies and in particular T cells induced by the bivalent vaccine. Compared to antibodies, COVID-19 virus can hardly evade from the T cells. Indeed, the findings reported in this paper indicate that although Omicron JN.1 evaded from the neutralizing antibodies elicited by the mRNA vaccine, T cell response remained largely intact against the JN.1. T cells induced by the bivalent mRNA vaccine were also barely affected by immune imprinting, a phenomenon that negatively affects updated vaccines in generating effective antibodies against new COVID-19 and flu virus strains. In conclusion, the findings reported in this paper support the “old” bivalent mRNA vaccines could still protect people from new Omicron strain infections by harnessing T cells, which was robustly elicited by the vaccine.

In the second paper that was published in Plos One, https://doi.org/10.1371/journal.pone.0314061, another vaccination strategy to deal with the rapid mutation of COVID-19 virus was explored. A tri-antigenic COVID-19 mRNA vaccine was designed and manufactured at PT. This vaccine contains mRNA encoding two additional proteins of COVID-19 virus besides spike, nucleocapsid (N) and membrane (M) proteins (All currently approved COVID-10 vaccines only target spike). Compared to spike, N and M proteins are much less mutated in COVID-19 virus and thus attractive targets for development of next generation of COVID-19 vaccine, which can protect against multiple virus strains, old and new. Our collaborators at Sunnybrook Research Institute and University of Toronto tested the new tri-antigenic mRNA vaccine in mice as a booster dose (3rd dose) to mimic COVID-19 booster vaccination in humans. They found that the tri-antigenic mRNA vaccine was as effective as PT’s spike-only mRNA vaccine in inducing broadly neutralizing antibodies and protecting mice from infection by an Omicron strain that carries a different spike from that encoded by the vaccines. Interestingly, the dose of the spike mRNA in the tri-antigenic mRNA vaccine was half of that in the spike-only mRNA vaccine, suggesting the N and M protein encoded in the tri-antigenic mRNA vaccine also helped generate effective immune response against spike. Overall, these results indicate that the tri-antigenic mRNA vaccine provide an avenue to develop the next generation of broadly protective COVID-19 mRNA vaccines.

Congratulations to our collaborators and the Providence Therapeutics team!