SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates against Symptomatic Infection

Abstract

Previous COVID-19 vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 from COVID-19-unvaccinated persons with detectable anti-SARS-CoV-2 antibodies. Neutralizing and binding antibody concentrations were severalfold lower in the unvaccinated study population compared to published concentrations at 28 days postvaccination. In this convenience sample, ~88% of neutralizing and ~63 to 86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection; ~30% of neutralizing and 1 to 14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. Our study not only supports observations of infection-induced immunity and current recommendations for vaccination postinfection to maximize protection against COVID-19, but also provides a large data set of pre-COVID-19 vaccination anti-SARS-CoV-2 antibody concentrations that will serve as an important comparator in the current setting of vaccine-induced and hybrid immunity. As new SARS-CoV-2 variants emerge and displace circulating virus strains, we recommend that standardized binding antibody assays that include spike protein-based antigens be utilized to estimate antibody concentrations correlated with protection from COVID-19. These estimates will be helpful in informing public health guidance, such as the need for additional COVID-19 vaccine booster doses to prevent symptomatic infection. IMPORTANCE Although COVID-19 vaccine efficacy (VE) studies have estimated antibody concentrations that correlate with protection from COVID-19, how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. We assessed quantitative neutralizing and binding antibody concentrations using standardized assays on serum specimens collected from COVID-19-unvaccinated persons with detectable antibodies. We found that most unvaccinated persons with qualitative antibody evidence of prior infection had quantitative antibody concentrations that met or exceeded concentrations associated with 70% VE against COVID-19. However, only a small proportion had antibody concentrations that met or exceeded concentrations associated with 90% VE, suggesting that persons with prior COVID-19 would benefit from vaccination to maximize protective antibody concentrations against COVID-19.

Keywords: COVID-19; IgG; SARS-CoV-2; anti-SARS-CoV-2; antibody; correlate of protection; correlation; immune; immunity; neutralizing antibodies; protection; quantitative; standardized.

FIG 1

SARS-CoV-2 50% neutralizing antibody titer (NT₅₀) concentrations and anti-SARS-CoV-2 receptor binding domain (RBD) IgG concentrations for the overall convenience sample of 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 with detectable anti-SARS-CoV-2 antibodies on a qualitative assay and according to sex and age category. SARS-CoV-2 NT₅₀ concentrations in international units per milliliter (IU/mL) (A) and anti-SARS-CoV-2 RBD IgG concentrations in binding antibody units per milliliter (BAU/mL) (B) are shown. Horizontal bars represent geometric means, vertical error bars represent 95% confidence intervals, and dashed horizontal lines represent assay cutoff values for seropositivity. P values from t tests (for sex) and post hoc Tukey tests (for age class) are shown for each sex and age class comparison. Bolded P values denote statistical significance (P < 0.05). Dotted horizontal lines represent antibody concentrations associated with 70% and 90% ChAdOx1 (11) and mRNA-1273 (12) vaccine efficacy (VE). The percentage of sera with antibody concentrations that met or exceeded the concentrations represented by each of the horizontal dotted lines are shown below the charts.

FIG 2

Correlations between SARS-CoV-2 50% neutralizing antibody titer (NT₅₀) concentrations in international units per milliliter (IU/mL) and anti-SARS-CoV-2 receptor binding domain (RBD) IgG concentrations in binding antibody units per milliliter (BAU/mL) for the convenience sample of 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 with detectable anti-SARS-CoV-2 antibodies in a qualitative assay. (A) Overall comparison; (B) comparison by sex; (C) comparison by age class.

FIG 3

SARS-CoV-2 50% neutralizing antibody titer (NT₅₀) concentrations in international units per milliliter (IU/mL) and anti-SARS-CoV-2 receptor binding domain (RBD) IgG concentrations in binding antibody units per milliliter (BAU/mL) for the overall convenience sample of 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 with detectable anti-SARS-CoV-2 antibodies on a qualitative assay compared to 28 days post-COVID-19 vaccination concentrations in ChAdOx1 (11) and mRNA-1273 (12) VE study participants classified as not having COVID-19 during the follow-up period. (A) Median and interquartile range SARS-CoV-2 NT₅₀ concentrations for the overall convenience sample compared to concentrations in VE study participants who received the ChAdOx1 vaccine and were classified as not having COVID-19 during the follow-up period. (B) Geometric mean and 95% confidence interval SARS-CoV-2 NT₅₀ concentrations for the overall convenience sample compared to concentrations in VE study participants who received the mRNA-1273 vaccine and were classified as not having COVID-19 during the follow-up period. (C) Median and interquartile range anti-SARS-CoV-2 RBD IgG concentrations for the overall convenience sample compared to concentrations in VE study participants who received the ChAdOx1 vaccine and were classified as not having COVID-19 during the follow-up period. (D) Geometric mean and 95% CI anti-SARS-CoV-2 RBD IgG concentrations for the overall convenience sample compared to concentrations in VE study participants who received the mRNA-1273 vaccine and were classified as not having COVID-19 during the follow-up period. Horizontal bars represent medians or geometric means, and vertical error bars represent the interquartile range surrounding the median or 95% confidence intervals surrounding the geometric mean.