Abstract Title
Safety and Immunogenicity of mRNA-1403, a Multivalent Norovirus mRNA Vaccine, in Healthy Adults: Interim Results of a Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Trial
Presenter
Meklit Workneh, Moderna
Co-Author(s)
Till Schoofs, MD1; Brooke A. Bollman, PhD1; Kevin J. Mancini, MS1; Wenlin Yuan, MS, PhD1; Lauren Bailey, PhD1; Tin Bartholomew, MA1; Esther Levine, MD1; Katherine B. Carlson, PhD, MPH1; Alexander Rumyantsev, MD, PhD1; Meklit Workneh, MD, MPH1; Doran Fink, MD, PhD1; Jaap Oostendorp, PhD1
1 Moderna, Inc.; Cambridge, MA
Abstract Category
Vaccines and immunity
Abstract
Background
Norovirus (NoV) is a leading cause of acute gastroenteritis worldwide. Currently, there is no licensed NoV vaccine. Given NoV’s high genetic diversity, a multivalent vaccine approach is optimal. A trivalent mRNA-based NoV vaccine candidate (mRNA-1403), with mRNAs encoding for the major capsid protein (VP1) of 3 globally prevalent NoV genotypes (GII.4, GI.3 and GII.3) formulated in a lipid nanoparticle, is in development.
Methods
In this ongoing Phase 1/2, randomized, placebo-controlled, observer-blind, dose-ranging study, safety, reactogenicity, and immunogenicity of mRNA-1403 are being evaluated in healthy adults 18 to 80 years of age (NCT05992935).
Results
In Phase 1, 335 adults received 1 or 2 injections of mRNA-1403 or Placebo at 4 dose levels. mRNA-1403 was well-tolerated across all dose levels without safety concerns identified through 8 months of follow-up from first injection. A single injection of mRNA-1403 elicited robust levels of serum histo-blood group antigen (HBGA)-blocking antibodies and binding antibodies against vaccine-matched NoV genotypes at 1-month post-injection across all dose levels. In Phase 2, 616 adults received a single injection of 1 of 3 selected dose levels of mRNA-1403 or Placebo. Data in this larger sample size of younger and older adults through 1-month post-injection confirmed that a single-injection of all 3 dose levels of mRNA-1403 was well-tolerated, safe and immunogenic.
Conclusions
Results from this ongoing Phase 1/2 study show that mRNA-1403 was generally safe and well-tolerated, and induced antigen-specific immune responses at all dose levels evaluated. These results informed dose selection for a Phase 3 efficacy study in adults.
Norovirus (NoV) is a leading cause of acute gastroenteritis worldwide. Currently, there is no licensed NoV vaccine. Given NoV’s high genetic diversity, a multivalent vaccine approach is optimal. A trivalent mRNA-based NoV vaccine candidate (mRNA-1403), with mRNAs encoding for the major capsid protein (VP1) of 3 globally prevalent NoV genotypes (GII.4, GI.3 and GII.3) formulated in a lipid nanoparticle, is in development.
Methods
In this ongoing Phase 1/2, randomized, placebo-controlled, observer-blind, dose-ranging study, safety, reactogenicity, and immunogenicity of mRNA-1403 are being evaluated in healthy adults 18 to 80 years of age (NCT05992935).
Results
In Phase 1, 335 adults received 1 or 2 injections of mRNA-1403 or Placebo at 4 dose levels. mRNA-1403 was well-tolerated across all dose levels without safety concerns identified through 8 months of follow-up from first injection. A single injection of mRNA-1403 elicited robust levels of serum histo-blood group antigen (HBGA)-blocking antibodies and binding antibodies against vaccine-matched NoV genotypes at 1-month post-injection across all dose levels. In Phase 2, 616 adults received a single injection of 1 of 3 selected dose levels of mRNA-1403 or Placebo. Data in this larger sample size of younger and older adults through 1-month post-injection confirmed that a single-injection of all 3 dose levels of mRNA-1403 was well-tolerated, safe and immunogenic.
Conclusions
Results from this ongoing Phase 1/2 study show that mRNA-1403 was generally safe and well-tolerated, and induced antigen-specific immune responses at all dose levels evaluated. These results informed dose selection for a Phase 3 efficacy study in adults.