Effectiveness of the adjuvanted Sanofi/GSK (VidPrevtyn Beta) and Pfizer-BioNTech (Comirnaty Original/Omicron BA.4-5) bivalent vaccines against hospitalisation amongst adults aged 75 years and older in England, estimated using a test-negative case control study design

Abstract

BackgroundIn England, the Joint Committee for Vaccination and Immunisation recommended a spring 2023 booster programme for all adults aged 75 years and older and the immunosuppressed. The vaccines advised were the Sanofi/GSK AS03-adjuvanted monovalent beta variant (VidPrevtyn Beta) booster vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, the antibody levels generated by the Sanofi/GSK vaccine were comparable to levels generated by COVID-19 mRNA vaccines but to date there are no real-world data on the effectiveness or duration of protection of this vaccine.MethodsWe used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. The study period for tests contributing to all analyses was from 3rd April 2022 to 27th August 2023. Vaccine effectiveness was estimated relative to those who had received at least two doses prior to their spring booster, with their last dose being an autumn 2022 booster given at least 3 months prior.FindingsOverall, there were 14,174 eligible tests from hospitalised individuals aged 75 years and older, with 3,005 being cases and 11,169 being controls. Effectiveness against hospitalisation was highest in the period 9 to 13 days post vaccination for both manufacturers at about 50%; 43.6% (95% C.I.; 20.1 to 60.2%) and 56.4% (95% C.I; 25.8 to 74.4%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was some evidence of waning with a reduction to about 30% for both manufacturers 5-9 weeks post vaccination.InterpretationTogether, these results provide reassuring evidence that both the adjuvanted Sanofi/GSK and Pfizer BA.4-5 booster vaccines provided a good boost to protection against hospitalisation amongst adults aged 75 years and older. The finding that the adjuvanted vaccine targeting the now distant Beta strain had similar effectiveness to the mRNA vaccine targeting more closely matched Omicron sub-lineages BA.4-5 during a period of Omicron circulation may reflect improved protection due to the adjuvant in the Sanofi/GSK product.FundingNo external funding.

Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2

“…Unlike the structures reported for other recombinant spike trimers, where the protein is in a closed canonical conformation with all RBD down 25 , both Sanofi vaccine antigens are in an RBD-up conformation potentially allowing the display of a broader antigenic surface. This is particularly important for the Beta trimer where the antigen shows a canonical quaternary structure with two RBD in the up position and is consistent with the similar clinical effectiveness observed in the UK Spring vaccine campaign utilizing both Sanofi Vidprevtyn Beta and Pfizer Omicron bivalent booster vaccines 32 , 33 .…”

“…Here we demonstrate the Beta spike trimer in the Sanofi COVID booster vaccine has a preferential two RBD up conformation, providing twice the surface area of exposed RBD amino acids compared to the ancestral spike trimer booster vaccine. Three key mutations in the Beta spike RBD (K417N, E484A, and N501Y) are the target for two thirds of the most potent neutralizing antibodies identified from Beta SARS-CoV-2 infected individuals 32 , thus contributing to the broadly cross neutralizing immunogenicity demonstrated in the clinical development of the vaccine 12 , 13 and the real-world effectiveness against Omicron XBB.1.5 33 .…”

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: The RAVEN cohort study

“…Since completion of the RAVEN study, updated variant vaccines have been developed and have been shown to be effective as booster doses in the general population. 61,62 However, it is likely that immunocompromised and more vulnerable individuals will still not receive the same level of protection. It will be important to evaluate variant booster vaccines in subgroups of immunocompromised and vulnerable populations to identify the true effectiveness and assess the ongoing need for additional interventions for these individuals.…”