Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.
Level 2 - randomized trial
Phase 1 randomized dose-escalation trial with accompanying preclinical animal experiments
PubMed 28457665 · doi:10.1016/j.ymthe.2017.03.035
What was done
Preclinical studies evaluated lipid nanoparticle (LNP)-formulated, modified mRNA vaccines encoding hemagglutinin (HA) proteins of avian influenza H10N8 and H7N9 in mice, ferrets, and nonhuman primates using hemagglutination inhibition and microneutralization assays, alongside a lethal challenge model in mice and viral load measurements in ferrets. In humans, an interim analysis was conducted on a first-in-human, escalating-dose, Phase 1 randomized trial evaluating the immunogenicity and safety of the H10N8 mRNA vaccine.
What was found
Preclinically, vaccination generated rapid immune responses across all three animal species; a single dose of H7N9 mRNA prevented mortality in lethally challenged mice and reduced lung viral titers in ferrets. In the human Phase 1 trial, H10N8 mRNA vaccination resulted in very high seroconversion rates (exact numerical rates and titers not reported in abstract). Adverse events were predominantly mild to moderate, with a few severe events and no serious adverse events.
Why it matters
This study provided early proof-of-concept for the viability, rapid immunogenicity, and acceptable safety profile of LNP-encapsulated mRNA vaccines targeting pandemic-potential avian influenza strains in humans.
Limits
The abstract does not disclose exact sample sizes, numerical antibody titers, or specific adverse event counts. As an interim Phase 1 trial, human findings are restricted to surrogate immunogenicity endpoints rather than clinical efficacy against infection, and long-term durability was not assessed.
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- supports In 2017, clinical trials took place testing an mRNA-based vaccine for influenza and injecting mRNA into the heart to treat heart failure.