Woldemeskel, Bezawit A., Garliss, Caroline C., Aytenfisu, Tihitina Y., Johnston, Trevor S., Beck, Evan J., Dykema, Arbor G., Frumento, Nicole, Wright, Desiree A., Yang, Andrew H., Damanakis, Alexander, I, Laeyendecker, Oliver, Cox, Andrea L., Mostafa, Heba H., Karaba, Andrew H. and Blankson, Joel N. (2022). SARS-CoV-2-specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge. JCI Insight, 7 (10). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

BACKGROUND. Breakthrough SARS-CoV-2 infections in vaccinated individuals have been previously associated with suboptimal humoral immunity. However, less is known about breakthrough infections with the Omicron variant. METHODS. We analyzed SARS-CoV-2???specific antibody and cellular responses in healthy vaccine recipients who experienced breakthrough infections a median of 50 days after receiving a booster mRNA vaccine with an ACE2 binding inhibition assay and an ELISpot assay, respectively. RESULTS. We found that high levels of antibodies inhibited vaccine strain spike protein binding to ACE2 but that lower levels inhibited Omicron variant spike protein binding to ACE2 in 4 boosted vaccine recipients prior to infection. The levels of antibodies that inhibited vaccine strain and Omicron spike protein binding after breakthrough in 18 boosted vaccine recipients were similar to levels seen in COVID-19???negative boosted vaccine recipients. In contrast, boosted vaccine recipients had significantly stronger T cell responses to both vaccine strain and Omicron variant spike proteins at the time of breakthrough. CONCLUSION. Our data suggest that breakthrough infections with the Omicron variant can occur despite robust immune responses to the vaccine strain spike protein. FUNDING. This work was supported by the Johns Hopkins COVID-19 Vaccine-related Research Fund and by funds from the National Institute of Allergy and Infectious Disease intramural program as well as awards from the National Cancer Institute (U54CA260491) and the National Institutes of Allergy and Infectious Disease (K08AI156021 and U01AI138897).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Woldemeskel, Bezawit A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garliss, Caroline C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aytenfisu, Tihitina Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnston, Trevor S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Evan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dykema, Arbor G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frumento, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, Desiree A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Andrew H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damanakis, Alexander, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laeyendecker, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, Andrea L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mostafa, Heba H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karaba, Andrew H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blankson, Joel N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-682573
DOI: 10.1172/jci.insight.159474
Journal or Publication Title: JCI Insight
Volume: 7
Number: 10
Date: 2022
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Place of Publication: ANN ARBOR
ISSN: 2379-3708
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68257

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