Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates

Abstract

The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine was no longer well-matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variants containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95% CI: 1.07-1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the rollout of future booster vaccination programmes.

Fig. 1. Possible comparisons between different SARS-CoV-2 vaccine immunogens.

A Chronology of the appearance of different SARS-CoV-2 variants and associated vaccine immunogens, and the comparisons made between different vaccine immunogens to induce neutralisation against future variants (coloured arrows). B Data extracted from identified papers could contribute to each of the comparisons outlined in (A). Lines connect paired cohorts from the same study. The centre lines of the boxes show the median; box limits show the interquartile range; and whiskers show the range of the data (outliers that are more than 1.5 times the interquartile ranges from the box edge are not shown).

Fig. 2. Fold rise in neutralisation titres to the XBB family variants after boosting with vaccines containing different booster immunogens.

Small numbers show the geometric mean of the fold rises for each immunogen. Comparisons across the top show p-values from two-sided unpaired t-tests. The centre lines of the boxes show the median; box limits show the interquartile range; and whiskers show the range of the data (excluding outliers that are more than 1.5 times the interquartile ranges from the box edge).

Fig. 3

PRISMA flow chart showing studies selected for inclusion in the meta-analysis.