ABSTRACT
BACKGROUND: We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses. METHODS: Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64â¯years for H10N8 study; 18-49â¯years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3â¯weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400⯵g and intradermal dose levels of 25 and 50⯵g were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6â¯months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay). RESULTS: H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (Nâ¯=â¯201), 100-µg IM dose induced HAI titersâ¯≥â¯1:40 in 100% and MN titersâ¯≥â¯1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titersâ¯>â¯1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (Nâ¯=â¯156), IM doses of 10, 25, and 50⯵g achieved HAI titersâ¯≥â¯1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titersâ¯≥â¯1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100⯵g IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50⯵g). Significant cell-mediated responses were not detected in either study. CONCLUSIONS: The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043.