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.