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. 2024 Mar 19:15:1287504.
doi: 10.3389/fimmu.2024.1287504. eCollection 2024.

Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection

Emilie Goguet  1   2 , Cara H Olsen  3 , William A Meyer 3rd  4 , Sara Ansari  4 , John H Powers 3rd  5 , Tonia L Conner  1 , Si'Ana A Coggins  1   2 , Wei Wang  6 , Richard Wang  6 , Luca Illinik  2   7 , Margaret Sanchez Edwards  2   7 , Belinda M Jackson-Thompson  1   2 , Monique Hollis-Perry  8 , Gregory Wang  8   9 , Yolanda Alcorta  8   9 , Mimi A Wong  8   9 , David Saunders  10 , Roshila Mohammed  2   7 , Bolatito Balogun  2   7 , Priscilla Kobi  2   7 , Lakeesha Kosh  2   7 , Kimberly Bishop-Lilly  11 , Regina Z Cer  11 , Catherine E Arnold  11   12 , Logan J Voegtly  11   13 , Maren Fitzpatrick  11   13 , Andrea E Luquette  11   13 , Francisco Malagon  11   13 , Orlando Ortega  2   7 , Edward Parmelee  2   7 , Julian Davies  2   7 , Alyssa R Lindrose  1   2 , Hannah Haines-Hull  1   2 , Matthew S Moser  1   2 , Emily C Samuels  1   2 , Marana S Rekedal  1   2 , Elizabeth K Graydon  1   2 , Allison M W Malloy  14 , David R Tribble  7 , Timothy H Burgess  7 , Wesley Campbell  15 , Sara Robinson  15 , Christopher C Broder  1 , Robert J O'Connell  7 , Carol D Weiss  6 , Simon Pollett  2   7 , Eric D Laing  1 , Edward Mitre  1
Affiliations

Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection

Emilie Goguet et al. Front Immunol. .

Abstract

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States.

Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires.

Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range.

Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

Keywords: COVID-19; SARS-CoV-2; correlates of immunity; respiratory infection; vaccination.

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Conflict of interest statement

SP, TB, and DT report that the USU IDCRP, a U.S. Department of Defense DoD Institution, and the HJF were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the USG COVID-19 response. Neither is related to the work presented here. Authors WM and SA were employed by the company Quest Diagnostics. Author JP was employed by company Leidos Biomedical Research, Inc. Authors LV, MF, AL and FM were employed by company Leidos. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Binding antibody serum levels against Wuhan-1 wild-type (WT) spike in research and commercial assays. (A) Comparison of anti-Wuhan-1 wild-type (WT) spike (S) IgG serum levels between the uninfected group and the post-vaccine infection (PVI) group. p-Values determined using the Mann–Whitney U test (p = 0.0098). (B) Percentages of uninfected vs. PVI participants depending on the anti-S IgG serum levels determined using the research assays. (C) Comparison of anti-S (WT) IgA serum levels between the uninfected group and the PVI group. p-Values determined using the Mann–Whitney U test (p = 0.1167). (D) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and Roche Elecsys® Anti-SARS-CoV-2 S assay anti-RBD (WT) total bAb serum levels (BAU/mL) in 171 samples (Spearman ρ = 0.8239; p < 0.0001). (E) Comparison of anti-RBD (WT) total bAb serum levels between the uninfected group and the PVI group using the Roche Elecsys® Anti-SARS-CoV-2 S assay. p-Values determined using the Mann–Whitney U test (p = 0.2138). (F) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and Siemens ADVIA Centaur® sCOVG assay anti-RBD (WT) IgG serum levels (BAU/mL) in 171 samples (Spearman ρ = 0.6929; p < 0.0001). (G) Comparison of anti-RBD (WT) IgG serum levels between the uninfected group and the PVI group using the Siemens ADVIA Centaur® sCOVG assay. p-Values determined using the Mann–Whitney U test (p = 0.4936). Dots indicate results from individual participants, and bars indicate geometric mean with 95% confidence intervals (CIs) in panels (A, C, E, G). Serum samples available for analysis: PVI group, n = 31; uninfected group, n = 140. **p < 0.01; ns, not significant.
Figure 2
Figure 2
Binding antibody serum levels against Omicron subvariant BA.1 spike in research assays and correlation with protection against SARS-CoV-2 post-vaccine infection. (A) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and research assay anti-S (BA.1) IgG serum levels (AU/mL) in 171 samples (Spearman ρ = 0.8411; p < 0.0001). (B) Comparison of anti-S (BA.1) IgG serum levels between the uninfected group and the post-vaccine infection (PVI) group. p-Values determined using the Mann–Whitney U test (p = 0.04). (C) Correlation between research assay anti-S (BA.1) IgG serum levels (AU/mL) and total FLU-PRO plus symptom scores (n = 31; Spearman ρ = −0.34; p = 0.0613). (D) Correlation between research assay anti-S (BA.1) IgG serum levels (AU/mL) and total symptom duration of any symptom in days (n = 31; Spearman ρ = −0.4597; p = 0.0093). Dots indicate results from individual participants. *p < 0.05.
Figure 3
Figure 3
Total FLU-PRO plus symptom scores and average scores for each symptom domain in the post-vaccine infection group. (A) Total FLU-PRO plus symptom scores for each participant in the post-vaccine infection (PVI) group (n = 32) and average scores for each symptom domain. The dashed line represents the average score of 5.9. (B) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and total FLU-PRO plus symptom scores (n = 31; Spearman ρ = −0.3859; p = 0.032). (C) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and total symptom duration of any symptom in days (n = 31; Spearman ρ = −0.5273; p = 0.0023). Dots indicate results from individual participants.
Figure 4
Figure 4
Binding antibody saliva levels against WT spike. (A) Comparison of anti-S (WT) IgG saliva levels between the uninfected group and the post-vaccine infection (PVI) group. p-Values determined using the Mann–Whitney U test (p = 0.2786). (B) Comparison of anti-S (WT) IgA saliva levels between the uninfected group and the PVI group. p-Values determined using the Mann–Whitney U test (p = 0.6579). (C) Percentages of uninfected vs. PVI participants depending on the anti-S (WT) IgG saliva levels. (D) Percentages of uninfected vs. PVI participants depending on the anti-S (WT) IgA saliva levels. (E) Correlation between research assay anti-S (WT) IgG serum levels (BAU/mL) and anti-S (WT) IgG saliva levels (AU/mL) (n = 175; Spearman ρ = 0.5536; p < 0.0001). (F) Correlation between research assay anti-S (WT) IgA serum levels (AU/mL) and anti-S (WT) IgA saliva levels (AU/mL) (n = 175; Spearman ρ = 0.3405; p < 0.0001). Dots indicate results from individual participants, and bars indicate geometric mean with 95% confidence intervals (CIs) in panels (A, B). Saliva samples available for analysis: PVI group, n = 32; uninfected group, n = 144. ns, not significant.
Figure 5
Figure 5
Pseudovirus neutralization ID50 titers against D614G, Delta variant B.1.617.2, and Omicron subvariants BA.1 and BA.1.1. Neutralization assays used lentiviral pseudoviruses bearing SARS-CoV-2 spike proteins from D614G, Delta variant B.1.617.2, or Omicron subvariants BA.1 and BA.1.1. p-Values determined using the Mann–Whitney U test (D614G, p = 0.1443; B.1.617.2, p = 0.0894; BA.1, p = 0.0313; BA.1.1, p = 0.021). Dots indicate results from individual participants, and bars represent geometric mean titers (GMTs) with 95% confidence intervals (CIs), and GMTs are indicated. Serum samples available for analysis: post-vaccine infection (PVI) group, n = 31; uninfected group, n = 140. *p < 0.05; ns, not significant.
Figure 6
Figure 6
Risk exposure and precautionary measure scores were calculated for the workplace and home. Risk exposure and precautionary measure scores were obtained during the visit following the Fall, 2021 research clinic visit (January to March, 2022). (A) Work risk score (WRS), calculated from three questions [uninfected, n = 140; post-vaccine infection (PVI), n = 32]; work precautionary score (WPS), calculated from three questions (uninfected, n = 134; PVI, n = 31); home risk score (HRS), calculated from four questions (uninfected, n = 140; PVI, n = 32); home precautionary score (HPS), calculated from five questions (uninfected, n = 140; PVI, n = 32). (B) HRS 1–2 represents questions 1 and 2 of the HRS category (COVID-19 exposure in households). HRS 3–4 represents questions 3 and 4 of the HRS category (out-of-the-house activities and social gatherings). p-Values determined using the Mann–Whitney U test (WRS, p = 0.3797; WPS, p = 0.9745; HRS, p < 0.0001; HPS, p = 0.6852; HRS 1-2, p < 0.0001; HRS 3-4, p = 0.9228). Dots indicate results from individual participants, and bars indicate mean with standard deviation. ****p < 0.0001; ns, not significant.
Figure 7
Figure 7
Odds ratios are unadjusted and adjusted for non-immunological factors. Odds ratios (ORs) represent the relative change in the odds of post-vaccine infection corresponding to an increase in the independent variable of 1/10 of its range (except for the odds ratio for “Female”). (A) Unadjusted odds ratios. (B) The pre-Omicron wave covariates were adjusted for age, sex, and home risk score (non-immunological factors). CI, confidence interval; ID50, 50% inhibitory dilution; BAU, binding antibody units; AU, arbitrary units.
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