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 5

Antibody responses to the Alpha variant correlate well with each other but correlate poorly with measures of T cell-mediated immunity.

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Antibody responses to the Alpha variant correlate well with each other b...
The correlation between various measures of humoral and cell-mediated immunity to the Alpha variant were assessed separately for (A) early FV-HC; (B) late FV-HC; (C) PV-Is; and (D) FV-Is. Scatter plots and trendlines are shown in the lower half of matrices, and correlation coefficients, color coded by the strength of the correlation, are shown in the upper half of the matrices. For cell-based measures, data shown is the ratio of SFUs per million for treated to untreated cells, transformed on a log10 scale.