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
; 37(25): 3326-3334, 2019 05 31.
Article
en En
| MEDLINE
| ID: mdl-31079849
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¯140 in 100% and MN titersâ¯≥â¯120 in 87.0% of participants. The 25-µg intradermal dose induced HAI titersâ¯>â¯140 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¯140 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titersâ¯≥â¯120 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Viral
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Vacunas contra la Influenza
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Gripe Humana
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Inmunogenicidad Vacunal
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Vaccine
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos