archives@tulane.edu / Infectious diseases are one of the leading causes of morbidity and mortality in humans. Vaccines are one of the best tools to protect against pathogens; however, there remains room for improvement in vaccine design. In particular, different adjuvants can be used to improve or alter the efficacy of vaccines. We hypothesize that adjuvant choice can be used to specifically modify the antigen- specific B cell response and target the response to mucosal tissues. Using an Ova- specific B cell tetramer to track the B cell response, we discovered that the adjuvant double mutant heat labile toxin (dmLT) from E. coli induced the greatest proliferation and activation of Ova-specific B cells two weeks after a single intramuscular or intradermal injection when compared to Ova with no adjuvant. Interestingly, anti-Ova IgG titers plateaued five weeks after the intradermal injection but was still increasing eight weeks after an intramuscular injection. Consistent with previous T cell data, dmLT was able to provoke antigen-specific B cells to express the mucosal homing marker a4b7 and induced residence of vaccine-specific B cells in the Peyer’s patches, lamina propria of large intestines, and lungs. This property was unique to dmLT as the adjuvant CpG was not able to induce similar tissue residence of Ova-specific B cells. Additionally, when dmLT was compared to the aluminum salt-based adjuvant (alum), that is used in the most vaccines, dmLT is able to enhance the antigen-specific B cell response more than alum regardless of route or quantity of injections. We also determined that dmLT produced a higher level of anti-Ova IgG compared to alum. Finally, we showed that combining dmLT with another adjuvant, monophosphoryl lipid A (MPL-A), improved proliferation and activation of antigen-specific B cells and generated higher amounts of Ova-specific IgG compared to any of the single adjuvants alone. Interestingly, while dmLT was a more effective at activating B cells, MPL-A induced higher titers of antibodies than dmLT. These studies present the first time that antigen-specific B cells have been found in mucosal tissues following parenteral immunization as well as provide insight into the effects that combining adjuvants have on B cells. / 1 / John Timothy Prior
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_121845 |
| Date | January 2023 |
| Contributors | Prior, John (author), (author), McLachlan, James (Thesis advisor), School of Medicine Microbiology and Immunology (Degree granting institution), NULL (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 182 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
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