"Adaptive Immune Profiling of Sin Nombre Hantavirus and Severe Acute Re" by Tonilynn M. Baranowski
 

Biomedical Sciences ETDs

Publication Date

Summer 7-30-2024

Abstract

Hantaviruses are causative agents of potentially fatal respiratory illness and/or organ failure in humans worldwide. In the United States, the predominant hantavirus species, Sin Nombre hantavirus (SNV), causes a severe disease pathology, called hantavirus cardiopulmonary syndrome (HCPS). Infection with SNV and subsequent clinical manifestations of HCPS lends itself to case fatality rates approaching 40%, even under supportive care. This is partially due to the lack of FDA-approved vaccines and antivirals, in addition to a deficit in our knowledge regarding the human immune response to SNV. Further investigation of the adaptive immune response may reveal key targets to mediate disease outcome. In this study, we aim to profile the long-lasting humoral and cellular immune responses in convalescent SNV patients. To identify benchmarks of the adaptive immune response to SNV, we collected blood samples from 13 patients, 3 acute and 10 convalescent, who presented with the diagnostic criteria for SNV infection. Antibody functionality was studied utilizing assays that quantitate antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity activity. The ADCC results demonstrated antibody functionality, in patients up to 14 years post infection, with no significant difference between acute and convalescent samples. Neutralizing antibody titers were present in all patients, up to 24 years post infection, and, similarly, revealed no significant difference between acute and convalescent samples. These data strongly suggest that SNV antibodies are multifunctional and are long-lived. Ongoing studies will focus on assessing SNV-specific polyfunctional memory T cell responses to define the cellular immune profile to SNV.

Keywords

Sin Nombre hantavirus, SNV, adaptive immune response, antibodies, Fc-mediated effector antibody function, antibody dependent cellular cytotoxicity

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Dr. Judy Cannon

Second Committee Member

Dr. Steven Bradfute

Third Committee Member

Dr. Alison Kell

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