Feldman RA, et al. 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. Vaccine. 2019 May 9.
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.
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.
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