Preventing COVID-19 in at-risk populations: moving toward next-generation mRNA-1283 COVID-19 vaccine to address current challenges

Expert Rev Vaccines. 2026 Dec;25(1):2632657. doi: 10.1080/14760584.2026.2632657. Epub 2026 Mar 3.

Abstract

Introduction: Next-generation COVID-19 vaccines hold promise to reduce severe outcomes in populations most at risk. While the original mRNA COVID-19 vaccine, mRNA-1273, targets the full-length SARS-CoV-2 spike protein, mRNA-1283 is a novel next-generation mRNA COVID-19 vaccine that specifically targets immunodominant domains within the spike protein.

Areas covered: This review summarizes literature on the development of mRNA-1283, from its design and preclinical evaluation to phase 1-3 clinical trial findings, with a particular focus on immunogenicity and efficacy in at-risk populations, specifically older adults and adults with comorbidities. The potential public health impact of this next-generation vaccine is explored, along with ongoing challenges facing COVID-19 vaccination.

Expert opinion: Phase 1-3 clinical trials demonstrated that mRNA-1283 was well-tolerated and no safety concerns were identified. Furthermore, mRNA-1283 demonstrated higher point estimates of immunogenicity and relative vaccine efficacy than mRNA-1273, including among older adults and individuals with underlying conditions who are most susceptible to severe COVID-19. Initial modeling studies indicate that mRNA-1283 could prevent more hospitalizations than current COVID-19 vaccines. Evidence to date suggests that the novel next-generation mRNA-1283 vaccine holds promise to advance progress in reducing the ongoing burden of COVID-19 across vulnerable populations.

Keywords: COVID-19; SARS-CoV-2; mRNA; mRNA-1283; vaccination; vaccine.

Publication types

  • Review

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Humans
  • Immunogenicity, Vaccine
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccine Efficacy
  • Vaccines, Synthetic / immunology

Substances

  • COVID-19 Vaccines
  • 2019-nCoV Vaccine mRNA-1273
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Vaccines, Synthetic