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.

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. ClinicalTrials.gov NCT03076385 and NCT03345043.

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV-15) compared to PCV-13 in healthy older adults.

BACKGROUND: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) were evaluated in adults ≥ 50 years (V114-006; NCT02547649). METHODS: A total of 690 subjects (230/arm) received a single dose of either PCV15 Formulation A, PCV15 Formulation B, or PCV13 and were followed for safety for 14 days postvaccination. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and Immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured immediately prior and 30 days postvaccination. RESULTS: Both PCV15 formulations had generally comparable safety profiles to PCV13. Baseline IgG GMCs and OPA GMTs were comparable across vaccination groups. At 30 days postvaccination, both PCV15 formulations induced serotype specific antibodies to all 15 serotypes in the vaccine. IgG GMCs and OPA GMTs in recipients of either PCV15 formulation were non-inferior (≤ 2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior (> 1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A. CONCLUSION: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.