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Teasing apart the immune response to a virus-derived adjuvant : insights into type 1 immunity inducing vaccine development / Devin Gail Fisher.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Fisher, Devin Gail, author.
- Language:
- English
- Subjects (All):
- Immunology.
- Cell and molecular biology--Penn dissertations.
- Penn dissertations--Cell and molecular biology.
- Local Subjects:
- Immunology.
- Cell and molecular biology--Penn dissertations.
- Penn dissertations--Cell and molecular biology.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (130 pages)
- Contained In:
- Dissertations Abstracts International 82-07B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2020.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Adjuvants boost and shape the immune response to killed and subunit vaccines. Currently there is a critical need for vaccine adjuvants that induce an immune response specific for intracellular pathogens, or type 1 immunity. As defective viral genomes are the primary immunostimulatory molecules during paramyxovirus infections, we tested whether a defective viral genome-derived oligonucleotide (DDO) induced type 1 immune responses when used as a vaccine adjuvant. We used a model influenza vaccine to examine the host response to DDO-adjuvanted vaccines. Using a combination of flow cytometry, ELISA, qPCR, and viral challenges we showed that DDO induces all the hallmarks of a type 1 immune response in mice. DDO induces IgG2c antibodies, Th1 CD4+ T-cells, and effector CD8+ T-cells. In addition to inducing robust type 1 immunity on its own, DDO synergizes with the mixed immunity inducing adjuvant AddaVax (the research equivalent of MF59) to induce even stronger type 1 immune responses. As CD8+ T-cell responses are difficult to induce in response to killed and subunit vaccination, we next examined the innate immune response to DDO to discover the requirements for CD8+ T-cell activation in response to vaccination. We determined that DDO requires the RNA sensor TLR3 and type I IFN signaling to induce type 1 conventional dendritic cell (cDC1) accumulation in the draining lymph node. cDC1 accumulation was required for CD8+ T-cell responses. Additionally, we show DDO induces a type I IFN and inflammatory response that is different from the double-stranded RNA mimic poly I:C. We have shown that DDO is a safe and effective type 1 immunity inducing adjuvant in mice. These studies illuminate aspects of the innate immune response that are required to induce a type 1 immune response and identify targets for adjuvant development and improvement.
- Notes:
- Source: Dissertations Abstracts International, Volume: 82-07, Section: B.
- Advisors: Lopez, Carolina B.; Eisenlohr, Laurence; Committee members: Paul Bates; Christopher Hunter; Drew Weissman.
- Department: Cell and Molecular Biology.
- Ph.D. University of Pennsylvania 2020.
- Local Notes:
- School code: 0175
- ISBN:
- 9798557047043
- Access Restriction:
- Restricted for use by site license.
- This item must not be sold to any third party vendors.
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