Predicting Vaccine Effectiveness for Hospitalization and Symptomatic Disease for Novel SARS-CoV-2 Variants Using Neutralizing Antibody Titers
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Abstract
The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8–4.4-fold and increased the risk of symptomatic disease 1.7–4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants.
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SciScore for 10.1101/2021.12.10.21267594: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:These results should be interpreted in the context of several important caveats. First, and foremost, neutralizing antibody titers are a surrogate for VE, and despite strong correlations between VE and neutralizing antibody titers (4-7), direct studies of VE are critical to determine the full extent of immune evasion of new variants. …
SciScore for 10.1101/2021.12.10.21267594: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:These results should be interpreted in the context of several important caveats. First, and foremost, neutralizing antibody titers are a surrogate for VE, and despite strong correlations between VE and neutralizing antibody titers (4-7), direct studies of VE are critical to determine the full extent of immune evasion of new variants. Specifically, our analyses assume that differences in disease severity of variants are correlated with differences in neutralizing antibody titers. Whether this will hold across the 40-fold reduction in neutralizing antibody titers is highly uncertain. Second, the extent of Omicron immune evasion is so large relative to previous variants (40-fold vs 7-fold for Beta), and VE estimates for the next most evasive variant, Beta, were so uncertain that we were unable to estimate vaccine-specific models to estimate VE for Omicron. Instead we assumed that differences in neutralizing antibody titers across vaccines and variants are suitable for estimating VE across variants. Third, the 40-fold reduction that we used for Omicron required extrapolation well outside of available data and prevented us from providing reliable VE estimates for Omicron for vaccinees with waned immunity. The Omicron variant of SARS-CoV-2 has grown rapidly in many countries. We have shown that the approximately 40-fold reduction in neutralizing antibody titers greatly erodes vaccine protection and increases the relative risk of infection and symptomatic disease more than four-fold...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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