Effectiveness and durability of a second COVID-19 booster against severe outcomes among older people in Norway: a population-based cohort study comparing mono- and bivalent booster doses.

BACKGROUND: Evidence on the durability of the protection of a fourth dose of a monovalent or bivalent messenger ribonucleic acid (mRNA) vaccine against coronavirus disease 2019 (COVID-19) among older people during the predominant Omicron period is needed. METHODS: We performed a population-based cohort study in Norway covering the time from 1 July 2022 to 15 January 2023, including individuals ≥75 years of age who had received at least a third dose. Using Cox proportional hazard models on severe COVID-19-associated outcome measures and all-cause mortality, we estimated the vaccine effectiveness of mono- and bivalent vaccines, comparing fourth- to third-dose recipients (>24 weeks ago). Vaccine status was included as a time-varying covariate and models were adjusted for potential confounders. RESULTS: We included 408 073 individuals. A fourth dose with either monovalent or bivalent mRNA vaccine showed increased protection against COVID-19-associated mortality relative to a third dose in individuals ≥75 years of age. We estimated a protective effect for the bivalent BA.1 vaccine [adjusted hazard ratio (aHR) 0.08, 95% CI 0.02-0.32] relative to the bivalent BA.4-5 (aHR 0.27, 95% CI 0.14-0.56) and a monovalent dose (aHR 0.34, 95% CI 0.26-0.45) 2-9 weeks after vaccination compared with recipients with a third dose >24 weeks ago. The increased protective effect waned with no added protection for the monovalent vaccine after 33 weeks compared with a third dose. CONCLUSIONS: Our results indicate an increased protective effect of a fourth dose against severe outcomes compared with a third dose, with decreasing effect with time since the last dose.

Characterization of meningococcal serogroup B outer membrane vesicle vaccines from strain 44/76 after growth in different media.

In this study, we evaluated the effect of the growth medium on the composition and immunogenicity of meningococcal outer membrane vesicle (OMV) vaccines after cultivation of the Norwegian serogroup B 44/76 vaccine strain in either Frantz' or modified Catlin-6 media (MC.6M). Differential proteomic analysis revealed that 97% of the OMV proteins maintained the same levels in the two preparations. However, a number of differentially expressed proteins, including TdfH, OpcA, OMP NMB0088, hypothetical NMB2134, lipoprotein NMB1126/1164 and NspA, increased significantly in OMVs produced from bacteria grown in the MC.6M. Together with increased lipopolysaccharide levels, the increased expression of these proteins was associated with significantly higher serum bactericidal titres in mice immunized with the MC.6M OMV vaccine. The high resolution two-dimensional separation of the OMVs on a large-format gel across a pH range of 3-11 resolved around 2000 protein spots from which 75 proteins were identified by mass spectrometry.