mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled phase 1 clinical trials
PubMed 31079849 · doi:10.1016/j.vaccine.2019.04.074
What was done
Two randomized, double-blind, placebo-controlled phase 1 clinical trials evaluated mRNA vaccines against avian influenza viruses in healthy adults. The H10N8 trial (Germany, ages 18–64) tested intramuscular doses (25, 50, 75, 100, 400 µg) and intradermal doses (25, 50 µg) administered 3 weeks apart. The H7N9 trial (USA, ages 18–49) tested intramuscular doses (10, 25, 50 µg) given 3 weeks or 6 months apart. Primary endpoints were safety and tolerability; secondary endpoints were humoral (hemagglutination inhibition [HAI], microneutralization [MN]) and cell-mediated immune responses (ELISPOT).
What was found
No vaccine-related serious adverse events occurred. In the H10N8 trial (N = 201), the 100-µg intramuscular dose achieved HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants, with seroconversion rates of 78.3% (HAI) and 87.0% (MN). The 25-µg intradermal dose achieved HAI titers > 1:40 in 64.7% compared with 34.5% for 25-µg intramuscular. In the H7N9 trial (N = 156), intramuscular doses of 10, 25, and 50 µg induced HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, and MN titers ≥ 1:20 in 100%, 100%, and 96.6%, respectively. The 50-µg H7N9 dose yielded seroconversion rates of 96.3% (HAI) and 100% (MN). Neither trial detected significant cell-mediated immune responses.
Why it matters
This study provides early proof-of-concept human data demonstrating that lipid-formulated mRNA vaccines can safely elicit robust neutralizing antibody titers against pandemic-threat avian influenza strains.
Limits
Both trials were early-phase single-center studies with small sample sizes across multiple dose cohorts, limiting power to detect rare adverse events. The studies only enrolled healthy young and middle-aged adults, precluding conclusions about older adults or high-risk populations. Protection was inferred from surrogate antibody titers without clinical efficacy or challenge data, and no meaningful T-cell responses were detected.
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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.