Unraveling the immune response to vaccination in mice and humans
Abstract/Contents
- Abstract
- The fundamental goal of vaccinations is the induction of robust and durable protective immunity against pathogens. The emergence of the SARS-CoV-2 virus, and its rapid mutation into immune-evasive variants, underscored the necessity for vaccines to confer long-lasting and cross-protective memory responses. While current vaccination strategies for respiratory viruses such as SARS-CoV-2 and influenza virus provide moderate protection, achieving durable sterilizing immunity against these pathogens has remained a major challenge. This dissertation explores two vaccination strategies that have the potential to enhance current immunization approaches. First, we investigate the potential of vaccine adjuvants as a strategy to augment the magnitude, durability and breadth of vaccine-induced immunity. In Chapter 2, using mouse models, we perform a comparative evaluation of the immune responses induced by diverse vaccine adjuvants in combination with a candidate COVID-19 vaccine antigen. In Chapter 3, we delve deeper into the adaptive immune responses induced by an adjuvanted COVID-19 vaccine in humans, with a particular focus on the breadth of the antibody responses in the presence and absence of the adjuvant. Our findings presented in these two chapters highlight the crucial role of vaccine adjuvants in enhancing the immune response to vaccination, elucidate the diversity of different adjuvant formulations, and provide evidence for the enhancement of cross-reactive immunity by investigating the clonal dynamics of B cells over the course of vaccination in humans. Second, we examine the incorporation of T cell memory in addition to humoral immunity as a vaccination strategy to enhance protection against infection. In Chapter 4, using influenza as a model, we investigate the role of T cell memory and antibody responses in contributing to protection either individually or in combination. We find that combining T cell memory with humoral immunity provides with superior protection against infection, highlighting T cells as attractive targets of vaccination. In Chapter 5, using a novel vaccination platform utilizing circular RNA encoding antigenic sequences, we induce robust CD8 T cell responses in mice, elucidating a novel candidate platform for T cell vaccines. Collectively, the findings in this thesis significantly enhance our understanding of the adaptive immune responses induced by vaccination. Our results underscore the pivotal role of adjuvants in shaping the immune response to vaccination, and reveal the contribution of T cell memory to protection against infection, presenting two promising strategies to address current challenges in vaccinology.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Grigoryan, Lilit |
|---|---|
| Degree supervisor | Pulendran, Bali |
| Thesis advisor | Pulendran, Bali |
| Thesis advisor | Davis, Mark |
| Thesis advisor | Lanz, Tobias |
| Thesis advisor | Martinez, Olivia |
| Degree committee member | Davis, Mark |
| Degree committee member | Lanz, Tobias |
| Degree committee member | Martinez, Olivia |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Lilit Grigoryan. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/vy878yx7401 |
Access conditions
- Copyright
- © 2023 by Lilit Grigoryan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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