No abstract

With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the ancestral vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.

With the ongoing evolution of the SARS-CoV-2 virus, variant-adapted vaccines are likely to be required. Given the challenges of conducting clinical trials against a background of widespread infection-induced immunity, updated vaccines are likely to be adopted based on immunogenicity data. We extended a modelling framework linking immunity levels and protection and fitted the model to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta and Omicron) to predict longer-term effectiveness against mild disease, hospitalisation and death. We use these model fits to predict the effectiveness of the Moderna bivalent vaccine (mRNA1273.214) against the Omicron variant using immunogenicity data. Our results suggest sustained protection against hospitalisation and death from the Omicron variant over the first six months following boosting with the monovalent vaccines but a gradual waning to moderate protection after 1 year (median predicted vaccine effectiveness at 1 year in 65+ age group: AZD1222 38.9%, 95% CrI 31.8%-46.8%; BNT162b2 53.3%, 95% CrI 49.1%-56.9%; mRNA-1273 60.0%, 95% CrI 56.0%-63.6%). Furthermore, we predict almost complete loss of protection against mild disease over this period (mean predicted effectiveness at 1 year 7.8% for AZD1222, 13.2% for BNT162b2 and 16.7% for mRNA-1273). Switching to a second booster with the bivalent mRNA1273.214 vaccine against Omicron BA.1/2 is predicted to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering a second booster with the monovalent mRNA1273 vaccine. Ongoing production and administration of variant-specific vaccines are therefore likely to play an important role in protecting against severe outcomes from the ongoing circulation of SARS-CoV-2.