Moderna, Inc.

To quantify preferences for an adult combination vaccine for influenza and COVID-19 (flu + COVID) compared with standalone influenza and COVID-19 vaccines.

This survey study used a series of direct-elicitation questions to assess preferences for a single-shot combination flu + COVID, standalone influenza, and standalone COVID-19 vaccines among US consumers (N = 601) and healthcare professionals (HCPs) (N = 299). Response frequencies described the proportion of each sample that would prefer a flu + COVID vaccine to standalone influenza and COVID-19 vaccines. A multivariate logit regression model explored how certain characteristics influenced the odds of selecting the flu + COVID vaccine over a standalone influenza vaccine.

Most consumers (398/601; 66.2%) and HCPs (250/298; 83.9%) preferred a flu + COVID vaccine to a standalone influenza vaccine. When not forced to choose between flu + COVID and standalone influenza vaccines, most consumers again selected the flu + COVID vaccine (62.3%); 14.7% would prefer separate standalone influenza and COVID-19 vaccines, 8.3% a standalone influenza vaccine only, 7.3% a COVID-19 vaccine only, and 7.4% neither vaccine. Consumers aged ≥50 years with a body mass index ≥40, those aged ≥65 years who previously received a COVID-19 vaccine, and those who had previously experienced severe impacts from influenza were more likely to choose a flu + COVID vaccine over a standalone influenza vaccine than were consumers without these characteristics. HCPs whose practice stocks high-dose influenza vaccines were more likely to choose the flu + COVID vaccine for patients aged ≥65 with no risk factors and patients aged 18-64 with ≥1 risk factor over the standalone influenza vaccine.

Results are subject to potential hypothetical, responder, selection, and information biases.

Most US consumers and HCPs would likely prefer a single-shot combination flu + COVID vaccine compared with standalone influenza and COVID-19 vaccines. Given the low COVID-19 vaccination coverage rates in the US, the availability of a combination flu + COVID vaccine could help increase COVID-19 vaccine coverage.

The safety, immunogenicity, and efficacy of the original formulation of the investigational mRNA-1010 vaccine for seasonal influenza were investigated in two randomized, active-controlled, phase 3 trials in adults (NCT05415462 and NCT05566639), and the results were used to evaluate hemagglutination inhibition (HAI) titers as correlates of risk and protection against influenza-like illness. mRNA-1010 (50-µg) demonstrated an acceptable reactogenicity and safety profile among the >14,000 adult participants vaccinated in both trials. The efficacy profile of mRNA-1010 was generally reflective of immunogenicity findings, with higher immune responses against influenza A strains and lower responses against influenza B strains relative to an active comparator (licensed inactivated influenza vaccine). An analysis of HAI titers as a correlate of protection against influenza infection provided support for its use as a surrogate endpoint for mRNA-1010, similar to licensed influenza vaccines. These findings support further optimization and development of mRNA-1010 against seasonal influenza.

Respiratory syncytial virus (RSV) is a common respiratory pathogen in children. After demonstrating safety and immunogenicity in adults, mRNA-1345 encoding the RSV prefusion (preF) stabilized F glycoprotein was investigated in children. This phase 1, randomized, observer-blind study assessed the safety and immunogenicity of mRNA-1345 (NCT04528719) in RSV-seropositive children (per microneutralization assay) aged 12-59 months and is part of a larger study in multiple populations. Participants received three doses of mRNA-1345 (15 μg or 30 μg) or placebo 56 days apart, with 12-month safety follow-up. Forty-six participants were randomized to receive mRNA-1345 15 μg (n = 15), mRNA-1345 30 μg (n = 16), or placebo (n = 15). mRNA-1345 was well tolerated at both dose levels. The most frequently reported solicited local adverse reaction (AR) was injection site tenderness (15 μg, 27.3%-50.0%; 30 μg, 53.3%-71.4%; placebo, 26.7%-33.3%). Most solicited systemic ARs were grade 1/2, with irritability/crying, loss of appetite, and sleepiness most frequently reported; reactogenicity did not increase with additional doses. Throughout the 12-month follow-up, no serious adverse events (AEs), deaths, AEs of special interest, or AEs leading to study discontinuation were reported. Three medically attended RSV infections were reported among placebo recipients. A single injection increased RSV-A and RSV-B neutralizing antibody titers (geometric mean fold rise [GMFR] over baseline: 15 μg, RSV-A = 18.9, RSV-B = 7.2; 30 μg, RSV-A = 34.9, RSV-B = 14.3) and RSV preF and postF binding antibody concentrations (GMFR: 15 μg, preF = 13.9, postF = 9.3; 30 μg, preF = 26.5, postF = 16.0); binding antibody responses were preF-biased. Subsequent doses did not further increase antibody levels. In conclusion, mRNA-1345 was well tolerated and boosted antibody levels in seropositive children aged 12-59 months.