Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection
Han-Sol Park, Janna R. Shapiro, Ioannis Sitaras, Bezawit A. Woldemeskel, Caroline C. Garliss, Amanda Dziedzic, Jaiprasath Sachithanandham, Anne E. Jedlicka, Christopher A. Caputo, Kimberly E. Rousseau, Manjusha Thakar, San Suwanmanee, Pricila Hauk, Lateef Aliyu, Natalia I. Majewska, Sushmita Koley, Bela Patel, Patrick Broderick, Giselle Mosnaim, Sonya L. Heath, Emily S. Spivak, Aarthi Shenoy, Evan M. Bloch, Thomas J. Gniadek, Shmuel Shoham, Arturo Casadevall, Daniel Hanley, Andrea L. Cox, Oliver Laeyendecker, Michael J. Betenbaugh, Steven M. Cramer, Heba H. Mostafa, Andrew Pekosz, Joel N. Blankson, Sabra L. Klein, Aaron A.R. Tobian, David Sullivan, Kelly A. Gebo
Han-Sol Park, Janna R. Shapiro, Ioannis Sitaras, Bezawit A. Woldemeskel, Caroline C. Garliss, Amanda Dziedzic, Jaiprasath Sachithanandham, Anne E. Jedlicka, Christopher A. Caputo, Kimberly E. Rousseau, Manjusha Thakar, San Suwanmanee, Pricila Hauk, Lateef Aliyu, Natalia I. Majewska, Sushmita Koley, Bela Patel, Patrick Broderick, Giselle Mosnaim, Sonya L. Heath, Emily S. Spivak, Aarthi Shenoy, Evan M. Bloch, Thomas J. Gniadek, Shmuel Shoham, Arturo Casadevall, Daniel Hanley, Andrea L. Cox, Oliver Laeyendecker, Michael J. Betenbaugh, Steven M. Cramer, Heba H. Mostafa, Andrew Pekosz, Joel N. Blankson, Sabra L. Klein, Aaron A.R. Tobian, David Sullivan, Kelly A. Gebo
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Research Article COVID-19 Infectious disease

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

Abstract

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

Authors

Han-Sol Park, Janna R. Shapiro, Ioannis Sitaras, Bezawit A. Woldemeskel, Caroline C. Garliss, Amanda Dziedzic, Jaiprasath Sachithanandham, Anne E. Jedlicka, Christopher A. Caputo, Kimberly E. Rousseau, Manjusha Thakar, San Suwanmanee, Pricila Hauk, Lateef Aliyu, Natalia I. Majewska, Sushmita Koley, Bela Patel, Patrick Broderick, Giselle Mosnaim, Sonya L. Heath, Emily S. Spivak, Aarthi Shenoy, Evan M. Bloch, Thomas J. Gniadek, Shmuel Shoham, Arturo Casadevall, Daniel Hanley, Andrea L. Cox, Oliver Laeyendecker, Michael J. Betenbaugh, Steven M. Cramer, Heba H. Mostafa, Andrew Pekosz, Joel N. Blankson, Sabra L. Klein, Aaron A.R. Tobian, David Sullivan, Kelly A. Gebo

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Figure 2

Measures of vaccine-induced humoral and cellular immunity decrease with time in HCs, with the exception of nAb to the parent strain.

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Measures of vaccine-induced humoral and cellular immunity decrease with ...
Plasma and PBMC samples were collected from fully vaccinated HCs, with no history of testing positive for COVID-19, either 7–14 days (early, n = 22) or 95–187 days (late, n = 15) after the second dose. Indirect ELISAs were used to measure IgG against S (A) and the S-RBD (B) from either the parent strain or Alpha variant viruses and are graphed as AUC values. (C) Microneutralization assays were also performed against the parent virus and Alpha variant, and AUC values are shown. (D) An IFN-γ ELISPOT was used to measure the SFUs per million PBMCs in response to SARS-CoV-2 S parent strain peptide pools. In A–C, the dashed lines indicate the limit of detection. Two-tailed, unpaired t tests were used to compare between groups, and paired 2-tailed t tests were used to compare outcomes on the same individuals. P values below 0.05 are shown, but since 4 comparisons were made in each panel, the Bonferroni correction for multiple comparisons suggests that only values below 0.0125 (i.e., 0.05/4) be considered statistically significant.