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Adjuvants and Age: Understanding Vaccine Response in Older Adults

Smith, Carson L.
http://orcid.org/0000-0003-2556-3128
http://rave.ohiolink.edu/etdc/view?acc_num=case1686304892147104

Abstract Details

2023, Doctor of Philosophy, Case Western Reserve University, Pathology.
Vaccination forms an immune memory to protect organisms from pathogens. Vaccination remains a critical part of the public health arsenal against infectious diseases. However, with age, the immune system experiences functional declines. This results in both increased susceptibility to disease as well as a decline in vaccine efficacy. To combat this, several vaccines targeted toward older adults use immune-boosting components like adjuvants. Adjuvants take advantage of the innate immune system to sense potential pathogens and promote effective adaptive responses to vaccines. However, it is not fully clear from mouse models 1) what innate immune responses lead to a protective adaptive response and 2) what a protective adaptive response looks like. In this thesis, we examine two adjuvanted vaccines shown to increase clinical protection in older adults. In chapter 3 of this thesis, we explore the model provided by the recombinant zoster vaccine (RZV). RZV is highly efficacious in older populations and utilizes the novel adjuvant AS01. We use techniques such as flow cytometry, RNA sequencing, and co-culture with T cells to analyze how AS01 affects human myeloid cells. We show that AS01 activates human myeloid cells, particularly monocytes, towards expression of inflammatory cytokines and costimulatory molecules. The other vaccine model examined is the adjuvanted trivalent influenza vaccine (aTIV), which has been shown in clinical trials to provide superior protection over unadjuvanted influenza vaccine. In chapter 4 of this thesis, we assess the humoral and cellular immunity induced by aTIV and TIV. We show that aTIV preferentially enhances anti-neuraminidase titers compared to TIV, potentially explaining its superior clinical protection in older populations. While age-related immune decline is demonstrable and results in increased clinical mortality, growing evidence suggests that aged immune systems can still respond to stimuli under the optimal circumstances. This thesis explores the mechanisms and vaccine outcomes of two vaccines that contain adjuvants and were developed for use in older adults. By better understanding adjuvants that have proven efficacy, we can better understand how adjuvants provide protection in a vulnerable population. This research can help us develop novel adjuvants for vaccines in the ongoing public health battle against infectious diseases.
Donald Anthony (Committee Chair)
David Canaday (Advisor)
Clive Hamlin (Committee Chair)
Carlos Subauste (Committee Member)
Cheryl Cameron (Committee Member)
216 p.
Immunology; Pathology
AS01; MF59; adjuvants; immunity; vaccination; human aging; immunosenescence; RNA sequencing; T cells; influenza; shingles; T cells; cellular immunity; humoral immunity

Recommended Citations

Citations

  • Smith, C. L. (2023). Adjuvants and Age: Understanding Vaccine Response in Older Adults [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1686304892147104

    APA Style (7th edition)

  • Smith, Carson. Adjuvants and Age: Understanding Vaccine Response in Older Adults. 2023. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1686304892147104.

    MLA Style (8th edition)

  • Smith, Carson. "Adjuvants and Age: Understanding Vaccine Response in Older Adults." Doctoral dissertation, Case Western Reserve University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=case1686304892147104

    Chicago Manual of Style (17th edition)

case1686304892147104
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© 2023, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
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