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J Infect Dis
. 2024 Jun 27:jiae329.
doi: 10.1093/infdis/jiae329. Online ahead of print. Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial
Jintanat Ananworanich 1 , Ivan T Lee 1 , David Ensz 2 , Lizbeth Carmona 1 , Kristi Schaefers 1 , Andrei Avanesov 1 , Daniel Stadlbauer 1 , Angela Choi 1 , Alicia Pucci 1 , Shannon McGrath 1 , Hsiao-Hsuan Kuo 1 , Carole Henry 1 , Ren Chen 1 , Wenmei Huang 1 , Raffael Nachbagauer 1 , Robert Paris 1
Affiliations
Background: Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)-based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a 3-part, first-in-human, phase 1/2 clinical trial.
Methods: In Parts 1-3 of this stratified, observer-blind study, adults aged ≥18 years old were randomly assigned to receive a single dose (6.25 µg to 200 µg) of mRNA-1010 or placebo (Part 1) or an active comparator (Afluria; Parts 2-3). Primary study objectives were assessment of safety, reactogenicity, and humoral immunogenicity of mRNA-1010, placebo (Part 1), or active comparator (Parts 2-3). Exploratory endpoints included assessment of cellular immunogenicity (Part 1) and antigenic breadth against vaccine heterologous (A/H3N2) strains (Parts 1-2).
Results: In all study parts, solicited adverse reactions were reported more frequently for mRNA-1010 than placebo or Afluria and most were grade 1 or 2 in severity. No vaccine-related serious adverse events or deaths were reported. In Parts 1-2, a single dose of mRNA-1010 (25 µg to 200 µg) elicited robust Day 29 hemagglutination inhibition (HAI) titers that persisted through 6 months. In Part 3, lower doses of mRNA-1010 (6.25 µg to 25 µg) elicited Day 29 HAI titers that were higher or comparable to Afluria for influenza A strains. Compared with Afluria, mRNA-1010 (50 µg) elicited broader A/H3N2 antibody responses (Part 2). mRNA-1010 induced greater T-cell responses than placebo at Day 8 that were sustained or stronger at Day 29 (Part 1).
Conclusions: Data support the continued development of mRNA-1010 as a seasonal influenza vaccine.
Clinicaltrials.gov identifier: NCT04956575 (https://clinicaltrials.gov/study/NCT04956575).
Keywords: influenza; messenger RNA; phase 1/2; randomized clinical trial; vaccine.
. 2024 Jun 27:jiae329.
doi: 10.1093/infdis/jiae329. Online ahead of print. Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial
Jintanat Ananworanich 1 , Ivan T Lee 1 , David Ensz 2 , Lizbeth Carmona 1 , Kristi Schaefers 1 , Andrei Avanesov 1 , Daniel Stadlbauer 1 , Angela Choi 1 , Alicia Pucci 1 , Shannon McGrath 1 , Hsiao-Hsuan Kuo 1 , Carole Henry 1 , Ren Chen 1 , Wenmei Huang 1 , Raffael Nachbagauer 1 , Robert Paris 1
Affiliations
- PMID: 38934845
- DOI: 10.1093/infdis/jiae329
Background: Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)-based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a 3-part, first-in-human, phase 1/2 clinical trial.
Methods: In Parts 1-3 of this stratified, observer-blind study, adults aged ≥18 years old were randomly assigned to receive a single dose (6.25 µg to 200 µg) of mRNA-1010 or placebo (Part 1) or an active comparator (Afluria; Parts 2-3). Primary study objectives were assessment of safety, reactogenicity, and humoral immunogenicity of mRNA-1010, placebo (Part 1), or active comparator (Parts 2-3). Exploratory endpoints included assessment of cellular immunogenicity (Part 1) and antigenic breadth against vaccine heterologous (A/H3N2) strains (Parts 1-2).
Results: In all study parts, solicited adverse reactions were reported more frequently for mRNA-1010 than placebo or Afluria and most were grade 1 or 2 in severity. No vaccine-related serious adverse events or deaths were reported. In Parts 1-2, a single dose of mRNA-1010 (25 µg to 200 µg) elicited robust Day 29 hemagglutination inhibition (HAI) titers that persisted through 6 months. In Part 3, lower doses of mRNA-1010 (6.25 µg to 25 µg) elicited Day 29 HAI titers that were higher or comparable to Afluria for influenza A strains. Compared with Afluria, mRNA-1010 (50 µg) elicited broader A/H3N2 antibody responses (Part 2). mRNA-1010 induced greater T-cell responses than placebo at Day 8 that were sustained or stronger at Day 29 (Part 1).
Conclusions: Data support the continued development of mRNA-1010 as a seasonal influenza vaccine.
Clinicaltrials.gov identifier: NCT04956575 (https://clinicaltrials.gov/study/NCT04956575).
Keywords: influenza; messenger RNA; phase 1/2; randomized clinical trial; vaccine.