Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach

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.

Fig. 1. Relationship between immunity levels and vaccine effectiveness.

Dose–response curves estimated from fitting to vaccine effectiveness data for the relationship between immunity level (IL, x-axis) and vaccine effectiveness against mild disease (A, D), hospitalisation (B, E) and death (C, F). Panels (A–C) show vaccine effectiveness against the Delta variant whilst panels (D–F) show vaccine effectiveness against the Omicron/BA.1 variant. The solid lines show the posterior median estimates and colour bands the 95% credible interval from our model fitted to the data on vaccine effectiveness against each variant. The dotted lines show the dose–response curves that would be projected using the original efficacy model presented in Khoury et al. which fitted the relationship between NAT and clinical endpoints against the ancestral virus and adjusting for the Delta and Omicron variants respectively by using the variant fold reductions (VFRs) from immunogenicity data reported in Cromer et al. and Khoury et al.^,.

Fig. 2. Projected vaccine effectiveness over time (in days) since the first vaccine dose for combinations of schedules for the Oxford/AstraZeneca AZD1222 (AZ), Pfizer-BioNTech BNT162b2 (PF) and Moderna mRNA-1273 (MD) vaccines.

Plots show immunity level (IL) in the left column, alongside effectiveness against mild disease, hospitalisation, and death on the right. Neutralisation and protection against the Delta and Omicron variants are shown in red and blue respectively. Seven regimens are shown: AZ delivered for three doses (AZ–AZ); two doses of AZ and a third dose of PF (AZ–PF); two doses of AZ and a third dose of MD (AZ–MD); PF delivered for three doses (PF-PF); two doses of PF and a third dose of MD (PF-MD); two doses of MD and a third dose of PF (MD–PF); and MD delivered for three doses (MD–MD). The solid lines show the posterior median fitted model estimate, and the points show mean estimates of vaccine effectiveness (and associated 95% confidence intervals) against three endpoints using data from England^–. Where estimates were only available stratified by age group, the data are from the 65+ age group. Sample sizes for each of the 143 data points vary according to the uptake of combinations and length of follow-up; these are provided in the data files.

Fig. 3. Model projected vaccine effectiveness over time following a fourth dose with either the vaccine against the ancestral strain (illustrated with Moderna mRNA.1273) or a variant-adapted vaccine, compared to only three doses.

A Vaccine effectiveness against mild disease, hospitalisation, and death, for three doses only (turqouise line), a fourth dose with the ancestral Moderna vaccine (orange line), a fourth dose with a variant-adapted vaccine against any strain (purple line), a variant-adapted vaccine against a homologous strain (pink line) and a variant-adapted vaccine against a heterologous strain (green line). The fourth dose is assumed to be administered 1 year after the third dose, such that estimates for the three-dose group are from 365 days post dose 3 through to 720 days. Estimates are based on the relationship between NAT and protection obtained from fitting to the Omicron BA.1 variant. B Proportion of dose four effectiveness (against mild disease, hospitalisation, and death) that is attributable to receiving any fourth dose (with either the ancestral or variant-adapted vaccine product), relative to the proportion of overall efficacy that is attributable to the variant-adapted product (rather than the ancestral) as the fourth dose, for one year following the fourth dose. This illustrates that administration of any fourth dose generates most of the incremental initial impact, but that the difference between administering the variant-adapted versus the ancestral vaccine becomes more substantial 6–12 months following vaccination.