The Synergistic Benefits of Combining Innate Immune Stimulators into Nanoparticle Adjuvants for Intradermal Vaccination
Abstract
The development of adjuvants suitable for intradermal vaccines has the potential to revolutionize vaccination strategies and improve global health. Intradermal vaccination (ID) administration targets the dermis, which is rich in immune cells that may elicit improved immunity than the conventional intramuscular (IM) route. Adjuvants, utilized in conjunction with ID vaccines, may further enhance immune responses by facilitating the targeted release of antigen and increasing the activation and recruitment of immune cells, notably dendritic cells (DCs), which can generate localized inflammation and initiate vaccine-mediated immunity. Combining innate immune stimulators may elicit synergistic immunological responses that can result in dosesparing and long- lasting protection, which is advantageous during pandemics when vaccine supply is limited or when targeting highly mutable pathogens. Intradermal vaccines and adjuvants have the possibility of expanding the applications of vaccines in various infectious diseases and immunotherapies, addressing the challenges presented by novel pathogens or malignancies, and ultimately advancing global public health. The research presented here reveals that Nano-11, a nanoparticle adjuvant derived from plants, can be combined with innate immune stimulators such as the TLR3 agonist poly(I:C) and the STING agonist cyclic-di-AMP to elicit enhanced immunity when delivered by ID vaccines. Intradermal vaccination with a combination adjuvant comprised of Nano-11 and a synthetic STING agonist, ADU-S100, was shown to have dose-sparing properties and produced superior immunity compared to intramuscular immunization in mice and in pigs. The Nano-11-based adjuvant technology also provided prophylactic and therapeutic protection in mouse models of lymphoma and melanoma. The Nano-11-based adjuvant platform for ID vaccines proposes to expand the availability of vaccines for infectious disease control and immunotherapy.
Degree
Ph.D.
Advisors
HogenEsch, Purdue University.
Subject Area
Public health|Immunology|Animal sciences|Bioinformatics|Cellular biology|Genetics|Morphology|Nanotechnology|Physiology|Therapy|Virology
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