TY - JOUR
T1 - Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection
AU - Park, Han Sol
AU - Shapiro, Janna R.
AU - Sitaras, Ioannis
AU - Woldemeskel, Bezawit A.
AU - Garliss, Caroline C.
AU - Dziedzic, Amanda
AU - Sachithanandham, Jaiprasath
AU - Jedlicka, Anne E.
AU - Caputo, Christopher A.
AU - Rousseau, Kimberly E.
AU - Thakar, Manjusha
AU - Suwanmanee, San
AU - Hauk, Pricila
AU - Aliyu, Lateef
AU - Majewska, Natalia I.
AU - Koley, Sushmita
AU - Patel, Bela
AU - Broderick, Patrick
AU - Mosnaim, Giselle
AU - Heath, Sonya L.
AU - Spivak, Emily S.
AU - Shenoy, Aarthi
AU - Bloch, Evan M.
AU - Gniadek, Thomas J.
AU - Shoham, Shmuel
AU - Casadevall, Arturo
AU - Hanley, Daniel
AU - Cox, Andrea L.
AU - Laeyendecker, Oliver
AU - Betenbaugh, Michael J.
AU - Cramer, Steven M.
AU - Mostafa, Heba H.
AU - Pekosz, Andrew
AU - Blankson, Joel N.
AU - Klein, Sabra L.
AU - Tobian, Aaron A.R.
AU - Sullivan, David
AU - Gebo, Kelly A.
N1 - Funding Information:
The authors gratefully acknowledge the study participants who generously gave of their time and samples. Funding was provided by Department of Defense grant W911QY2090012 Clinicaltrial.gov identifier NCT04323800 (to DS, KAG, AART, SLK, and AP); the NIH Center of Excellence in Influenza Research and Surveillance grant HHSN272201400007C (to AP, IS, and SLK); the NIH Specialized Center of Research Excellence grant U54AG062333 (to SLK, AP, HSP, and JRS); NIH NIAID grant 3R01AI152078-01S1 (to ALC and DS), Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH (to OL).
Publisher Copyright:
© 2022, Park et al.
PY - 2022/3/8
Y1 - 2022/3/8
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.155944
DO - 10.1172/jci.insight.155944
M3 - Article
C2 - 35104245
AN - SCOPUS:85125928731
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 5
M1 - e155944
ER -