Neutralising antibodies predict protection from severe COVID-19

Abstract

Background: Vaccine protection from COVID-19 has been shown to decline with time-since-vaccination and against SARS-CoV-2 variants. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Although Protection protection from symptomatic SARS-CoV-2 infection has been shown to be strongly correlated with neutralising antibody titres, however, this relationship has been is less well described for severe COVID-19. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Here we analyse whether neutralising antibody titre remains predictive of protection against severe COVID-19 in the face of waning neutralising antibody levels and emerging variants. Methods: We extracted data from 15 studies reporting on protection against a range of SARS-CoV-2 clinical endpoints ("any infection", "symptomatic infection" and "severe COVID-19"). We then estimated the concurrent neutralising antibody titres using existing parameters on vaccine potency, neutralising antibody decay, and loss of recognition of variants and investigated the relationship between neutralising antibody titre and vaccine effectiveness against severe COVID-19. Findings: Predicted neutralising antibody titres are strongly correlated with vaccine effectiveness against symptomatic and severe COVID-19 (Spearman rho = .94 and 0.63 respectively, p<.001 for both), consistent with previous estimates of the relationship between neutralisation and protection. Indeed 82% (137 of 167) of reported values of protection against severe COVID-19 across a range of vaccines and variants lie within the 95% confidence intervals of the published model. Interpretation: Neutralising antibody titres are predictive of vaccine effectiveness against severe COVID-19 including in realistic scenarios of waning immunity and viral variants. Funding: National Health and Medical Research Council (Australia), Medical Research Future Fund (Australia).

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

“…This may indicate that, while SARS-CoV-2 pathogenicity continues to fluctuate and may evolve away from the attenuated pathogenicity observed in BA.1 33 , the increased population immunity may keep disease severity relatively low 34 . Consistent with this, a recent analysis showed that neutralization capacity required to prevent severe disease is considerably lower than that required to prevent symptomatic infection 35 . In addition, there may be factors specific to the South African infection environment which reduce pathogenicity such as immunity from Beta infection combined with vaccination, which we found to broaden neutralization capacity against BA.4 and BA.5 23 .…”

Predicting the efficacy of variant-modified COVID-19 vaccine boosters

“…They included data from the Sanofi-GlaxoSmithKline, Moderna, and Pfizer-BioNTech vaccine constructs incorporating the Beta, Delta, or Omicron BA.1 spike proteins (either alone or in combination with each other or the ancestral variant spike proteins). We then used a validated model relating neutralisation titres to vaccine effectiveness to estimate the changes in vaccine protection under different booster regimens [9][10][11] .…”

“…Similar analyses can be used to predict comparative vaccine effectiveness against severe COVID-19 under the same assumption. A population with 50% protection from symptomatic infection is predicted to have 86.6% protection from severe COVID-19 9,11 . Boosting with an ancestral-based booster that increases neutralising antibody titres by 11-fold is expected to increase this to an average of 98% protection from severe disease over the six month period following boosting, and a variant-modified booster producing 1.5-fold higher neutralising antibody titres would increase protection to an average of 98.8% (i.e.…”

“…In addition, it relies on predicting vaccine efficacy from neutralisation titres. Although this approach has been validated in a number of contexts [9][10][11]14,15 , it cannot replace clinical studies of vaccine effectiveness. Thus, it will be important to validate these predictions in future.…”

Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses

“…It is however worth to note that the majority of SARS-CoV-2 neutralizing antibodies target the RBD region, whilst deletion of NTD antibodies have minimal impact on neutralization 28 . b) We have focused on neutralizing activity, which is the only known correlate of protection so far 1,29 . But it is likely that T cell responses 8 and non-neutralizing antibody and functions 9,10 also contribute to protection against severe disease.…”