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

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.