SARS-CoV-2 variants: levels of neutralisation required for protective immunity

Abstract A number of SARS-CoV-2 variants of concern (VOC) have been identified that partially escape serum neutralisation activity elicited by current vaccines. Recent studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. Here we integrate published data on in vitro neutralisation and clinical protection to understand and predict vaccine efficacy against existing SARS-CoV-2 variants. We find that neutralising activity against the ancestral SARS-CoV-2 is highly predictive of neutralisation of the VOC, with all vaccines showing a similar drop in neutralisation to the variants. Neutralisation levels remain strongly correlated with protection from infection with SARS-CoV-2 VOC (r=0.81, p=0.0005). We apply an existing model relating in vitro neutralisation to protection (parameterised on data from ancestral virus infection) and find this remains predictive of vaccine efficacy against VOC once drops in neutralisation to the VOC are taken into account. Modelling of predicted vaccine efficacy against variants over time suggests that protection against symptomatic infection may drop below 50% within the first year after vaccination for some current vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) has been shown to significantly increase neutralising antibodies. Our modelling suggests that booster vaccination should enable high levels of immunity that prevent severe infection outcomes with the current SARS-CoV-2 VOC, at least in the medium term.