(Other jurisdictions still use trivalent vaccines.) Some researchers have argued in favour of adding protection against additional strains, but doing so is logistically challenging with existing platforms.Ī team led by Norbert Pardi, from the University of Pennsylvania Perelman School of Medicine, and Raffael Nachbagauer, then at the Icahn School of Medicine at Mount Sinai, showed as much last year. The US relies on quadrivalent vaccines, containing haemagglutinin antigens (either purified from inactivated viruses or manufactured recombinantly) or live attenuated viruses that confer protection against four strains of influenza. “Every bit of time helps,” says Sally Mossman, head of GlaxoSmithKline's Vaccine R&D centre in the United States. This would enable them to make more informed decisions about what strains to include. The flexibility and speed of mRNA vaccine production mean that vaccine makers could wait longer to begin manufacturing - starting production in May, say, instead of February, for the northern hemisphere. Recombinant protein vaccines offer that same fidelity advantage, but the manufacturing process for these is comparatively cumbersome. By contrast, inactivated virus vaccines that are made in egg- and cell-based systems often suffer from sequence mutations that weaken their effectiveness.
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Because mRNA vaccines are manufactured synthetically, by encoding a target antigen sequence into a plasmid template, they offer high fidelity: encoded antigens exactly match the flu strains selected for each year’s vaccine. Some of these boil down to how the vaccines get made. (Seqirus acquired that platform from Novartis in 2015.) “Seeing an mRNA vaccine functional and generating such a robust response has somewhat derisked the outside concerns that people may have had around the general technology,” says Ethan Settembre, vice president of R&D at Seqirus.Īnd the potential benefits of mRNA for flu prophylaxis are many. Seqirus stayed out of the COVID-19 vaccine race, despite having a self-amplifying mRNA platform that delivers both the antigen-coding sequence and the replication machinery needed for the construct to copy itself inside the host cell. Then came the novel coronavirus, and “we literally swapped out flu coding sequences and swapped in SARS-CoV-2 sequences,” says Philip Dormitzer, head of viral vaccines research at Pfizer. Many of the leading mRNA-based flu contenders were working on flu vaccine candidates before the pandemic. “Or have we stumbled on something that’s functional for other viral glycoproteins as well?” Making it “Did we just get really incredibly lucky with COVID vaccines because of the antigen design and the immunodominancy of that protein?” asks Anna Blakney, an RNA bioengineer at the University of British Columbia. To impact the established market, the platform would need to find a more tolerogenic sweet spot, as well as offer major efficacy advantages.Īnd yet, it’s no sure thing that mRNA will prove capable of effectively delivering haemagglutinin glycoproteins, the main antigen found in flu vaccines. MRNA “is a tool that does offer some upside potential,” says Gary Nabel, former CSO of Sanofi, the founding director of the NIH’s Vaccine Research Center (VRC), and CEO of the stealth-stage immunotherapeutics company ModeX Therapeutics. These same symptoms can occur with approved flu shots, but typically are much milder in degree. Moderna and Pfizer/BioNTech’s authorized mRNA jabs for COVID-19 often cause sore arms, headaches, low-grade fevers and fatigue.
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All of these features could translate into greater immune protection.īut mRNA, at least when formulated in lipid nanoparticles (LNPs), is prone to tolerability issues. In theory, mRNA might make for a better product: elicited immune responses may be broader, expressed proteins should have better sequence fidelity, strain selection may be more accurate and the technology makes it easy to incorporate large numbers of antigens.
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Existing flu shots, whether built around inactivated viruses or recombinant proteins, typically offer only 40–60% protection from infection. Those vaccines are safe, but their efficacy leaves room for improvement. That’s because unlike with SARS-CoV-2 - for which there were no established medical interventions - nine flu jabs from four different vaccine manufacturers are already available in the United States alone.
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NIAID, National Institute of Allergy and Infectious Diseases saRNA, self-amplifying RNA.īut flu shots could also prove a more challenging test for mRNA than did COVID-19. AMRT-5400 and MRT-5401 rely on non-modified RNA.