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 18-64?years for H10N8 study; 18-49?years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3?weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400?μg and intradermal dose levels of 25 and 50?μg were evaluated. H7N9 IM 10-, 25-, and 50-μg dose levels were evaluated; 2-dose series 6?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 (N?=?201), 100-μg IM dose induced HAI titers?≥?1:40 in 100% and MN titers?≥?1:20 in 87.0% of participants. The 25-μg intradermal dose induced HAI titers?>?1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N?=?156), IM doses of 10, 25, and 50?μg achieved HAI titers?≥?1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers?≥?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?μg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50?μg). 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.