Seasonal quadrivalent influenza vaccine(Medicago, Inc.)

The development of modular virus-like particle (VLP) vaccine platforms with genetically inserted antigens in viral structural proteins shows great promise for advancing vaccine technology. However, the instability of many constructs leads to trial-and-error approaches, and the challenge of predicting stability based solely on amino acid sequences remains unresolved, yet highly appealing. This study evaluates the stability of wild-type murine polyomavirus (MPV) VP1 capsomeres and three engineered chimeric variants using molecular dynamics (MD) simulations and laboratory experiments. MD simulations, based on AlphaFold2 predictions and up-to-date all-atom force fields, accurately predicted the thermal stability and hydrophobicity of VP1-based capsomeres. Thermodynamic analysis revealed that binding energies from simulations reliably indicate thermal stability. Experiments and simulation results showed that inserts influence the stability of capsomeres differently, with larger insertions generally having a greater impact on the structures of capsomeres. This leads to increased intra-subunit distances and a higher proportion of flexible regions in the capsomere chassis. Capsomeres with less compact structures were found to have lower thermal stability. Specifically, the thermal transitional temperature (T_m) of the wild-type capsomeres was 46.9 °C, while the T_m values of the three chimeric derivatives were 42.0 °C, 38.8 °C, and 37.7 °C, reflecting a correlation between decreased thermal stability and reduced structural compactness. This research presents a robust approach for predicting the stability of novel VLP constructs based on amino acid sequences, potentially enhancing vaccine design by reducing failures, and suggests a shift towards minimal epitope insertions for improved stability.

The objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin inhibition (HI) and anti-Spike protein antibody responses in the Coad compared to Seq group. 497/498 participants were randomized and vaccinated in the Seq/Coad groups, respectively. The adjusted geometric mean titer/concentration ratios (95% confidence intervals) (Seq/Coad) for HI antibodies were 1.02 (0.89-1.18) for A/H1N1, 0.93 (0.82-1.05) for A/H3N2, 1.00 (0.89-1.14] for B/Victoria, and 1.04 (0.93-1.17) for B/Yamagata; and 0.98 (0.84-1.13) for anti-Spike antibodies, thus meeting the protocol-specified non-inferiority criteria. The most frequently reported adverse events in both groups were pain at the injection site and myalgia. The 2 groups were similar in terms of the overall frequency, intensity, and duration of adverse events. In conclusion, co-administration of mRNA-1273 booster vaccine with QIV in adults was immunologically non-inferior to sequential administration. Safety and reactogenicity profiles were similar in both groups (clinicaltrials.gov NCT05047770).