Spotlight on mRNA Post-Vaccination Reactions: Should First-Generation, Influenza mRNA Candidates Have a Place in U.S. Adult Seasonal Immunization?

OBJECTIVES: Comparable immune responses and considerably higher post-vaccination reactions have been displayed in trials studying first-generation seasonal influenza messenger ribonucleic acid (mRNA) compared to standard inactivated (egg-based or recombinant) vaccines. In United States (US) adults aged 18 to 64, we aimed to estimate the impact of reactogenicity and vaccine hesitancy from a payor’s perspective.

METHODS: Disease-transition model, capturing natural influenza health states in those infected and post-vaccination reactogenicity, in a one-year horizon. 2023 US demographics, epidemiology, and direct costs (US$) informed the model inputs. Equal acquisition cost and efficacy among vaccines was assumed. Grade 1&2, and Grade 3 reactions were classified as non-medically and outpatient attended, respectively. Results present scenarios of possible mRNA vaccine market shares (10%-30%), vaccination hesitancy (10%-30%) and observed mRNA reactions (baseline, +/-10%).

RESULTS: Augmenting 30% the market share of mRNA vaccines would lead to mean 4.4million (m, [range 3.9-4.9 ]) additional Grade 3 reactions (+191% [169-213] increase), equating in $48.8m (43.7-53.8) outpatient costs. 10% to 30% mRNA market shares result in 4.6m (3.5-5.8 [+6.5%]) to 13.9m (10.3-17.4m [+19%]) excess Grade 1&2 reactogenicity cases, respectively. Simultaneous variations in mRNA vaccination hesitancy and market shares would augment inpatient, outpatient and death cases as a result of lower vaccination coverage rates (VCR), raising mean direct costs $0.4m (+0.5%) to $3.6m (+4.8%), for the 10% and 30% scenarios, accordingly.

CONCLUSIONS: US adult seasonal influenza immunization with first-generation mRNA vaccine, as modeled with recent trial results, depicts substantial increases in post-vaccination reactions and direct costs when compared to licensed vaccines. Moreover, public hesitancy to vaccination may lead to excess use of healthcare resources as result of lower VCR. In the development of next generation seasonal influenza vaccines, the importance of the tolerability profile should not be undermined.