자료유형  

 학위논문

Control Number  

0016933735

International Standard Book Number  

9798380262941

Dewey Decimal Classification Number  

600

Main Entry-Personal Name  

Ravi, Subeksha Govinda Rajan.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pittsburgh., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(43 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Mailliard, Robbie;Marques, Ernesto T.;Rinaldo, Charles R.

Dissertation Note  

Thesis (M.Sc.)--University of Pittsburgh, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약The coronavirus pandemic is a major, ongoing public health crisis. COVID-19 has resulted in over 6 million deaths as of April 2023 according to WHO. The COVID-19 mRNA vaccine widely administered in the United States was based on the spike protein of the Washington strain of SARS-CoV-2. Several new studies have indicated that a phenomenon like original antigenic sin (where prior exposure to an antigen leads to an ineffective immune response against related antigens) might be occurring in COVID. In this study, we wanted to determine if a COVID-19 mRNA vaccine-induced memory CTLs cross-react with Delta/Omicron variant epitopes without target cell killing. To test this, we identified HLA-A2 restricted, CD8+ T-cell epitopes in the spike protein that differ between the Washington strain Vs the Delta and/or Omicron variants. We collected T-cells from HLA-A2 positive, MWCCS donors who were vaccinated but not naturally exposed to any variant of SARS-CoV-2 and expanded the antigen-specific T-cells ex-vivo. We then assessed the cross-reactive potential of these Washington variant spike-specific CD8+ T-cells (readout was optimized to detect CD8+ T-cells) against the variant peptides generated using IFNgamma ELISpot assay. We tested 14 peptide pairs and found that vaccine-induced CD8+ T-cells can cross-react with epitope variants. We also observed a decreased T-cell reactivity to the variant epitopes compared to the Washington epitopes in some cases and an increased T-cell reactivity to the variant epitopes compared to the Washington epitopes in some other cases. Another interesting observation was that MHC binding affinity and T-cell binding affinity did not always correlate with the T-cell responses (IFN-g production) observed. Our future efforts will be aimed at testing the killing capacity of the CTLs when exposed to variant-antigen expressing target cells. The findings from this study has laid a groundwork in determining the efficacy of the COVID vaccine and to determine if there is need for the development of a more efficacious COVID vaccine.

Subject Added Entry-Topical Term  

Infections.

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Monoclonal antibodies.

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Human immunodeficiency virus--HIV.

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COVID-19 vaccines.

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mRNA vaccines.

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Dendritic cells.

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Memory.

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Severe acute respiratory syndrome coronavirus 2.

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Cytotoxicity.

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Health care.

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Mutation.

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Cloning.

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Cytokines.

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Cohort analysis.

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Public health.

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Amino acids.

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Antigens.

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Pathophysiology.

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Drug dosages.

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Disease transmission.

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Cellular biology.

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Immunology.

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Pathology.

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Physiology.

Added Entry-Corporate Name  

University of Pittsburgh.

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:641331