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
| Autor: | Ӧrn Almarsson, Robert A Feldman, Michael Watson, Michael E Laska, Rainard Fuhr, Joseph J. Senn, Amilcar Mick Ribeiro, Tal Zaks, James G. Thompson, Igor Smolenov, Michael J. Smith, Lori Panther, Giuseppe Ciaramella, Hari S Pujar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent 030231 tropical medicine Antibodies Viral Influenza A Virus H7N9 Subtype Placebo Young Adult 03 medical and health sciences Immunogenicity Vaccine 0302 clinical medicine Double-Blind Method Influenza A Virus H10N8 Subtype Internal medicine Influenza Human medicine Humans 030212 general & internal medicine Seroconversion Adverse effect Hemagglutination assay Reactogenicity Dose-Response Relationship Drug General Veterinary General Immunology and Microbiology business.industry Immunogenicity Public Health Environmental and Occupational Health Middle Aged Healthy Volunteers Vaccination Infectious Diseases Tolerability Influenza Vaccines RNA Viral Molecular Medicine Female business |
| Zdroj: | Vaccine. 37:3326-3334 |
| ISSN: | 0264-410X 0307-6385 |
| DOI: | 10.1016/j.vaccine.2019.04.074 |
| Popis: | 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 . |
| Databáze: | OpenAIRE |
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