Document Type

Dissertation - Open Access

Award Date


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences

First Advisor

Hemachand Tummala


Many serious infections for which there are no existing vaccines, enter by a mucosal route such as HIV, influenza, and tuberculosis, etc. Therefore, designing safe and effective mucosal vaccines that elicit robust immune response at mucosal sites is still a major challenge without a safe mucosal adjuvant. Previously, our laboratory had discovered inulin acetate as a novel toll-like-receptor-4 agonist (adjuvant). The study in this dissertation explored the application of nanoparticles prepared with inulin acetate (InAc-NPs) as a vaccine adjuvant and delivery system for enhancing mucosal immunity. The rationale behind selecting InAc-NPs is their proven ability to activate strong systemic immunity along with an extensive understanding of their mechanisms of activation. In chapter-II, we have clearly established, through intranasal vaccinations in mice, that InAc-NPs could generate strong systemic and mucosal antibodies (IgG1, IgG2a, sIgA) and cytokine response that represents both humoral and cellular immunity. InAc-NPs efficiently delivered the antigen into macrophages as well as activated them to release inflammatory cytokines such as TNF-α, which have been attributed for robust immune response in mice. In chapter-III, the efficacy of InAc-NPs as a vaccine adjuvant in swine model was established for the first time along with the safety profile in mice. InAc-NPs are proficient in stimulation of swine PBMCs to secrete cytokines such as IL-6, IL12, and IFN-. Importantly, InAc-NPs carrying the influenza peptide (M2e) produced higher mucosal and systemic antibodies compared to unadjuvanted antigen in pigs. The study, for the first time, showed InAc as a vaccine adjuvant in pigs that will have significant implications in swine industry and human health. In chapter-IV, InAc-NPs were explored as a delivery system to carry TLR7 agonist C-563 to its target site in the phagosomes/endosomes of antigen presenting cells. InAc-NPs loaded with C563 provided a unique dual adjuvant and/or a delivery system for vaccines that require robust immune response such as cancer or influenza vaccines. In conclusion, we have demonstrated the ability of InAc-NPs as a robust vaccine adjuvant and a delivery platform that provides strong systemic and mucosal immunity, which will have significant implications in fighting challenging diseases such as HIV, influenza, cancer, and tuberculosis.


South Dakota State University


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Available for download on Thursday, April 28, 2022