Investigating the effects of adjuvanted vaccines on antibody production in Toll-like receptor 4 (TLR4) deficient mice 3027

Abstract Description Toll-like receptors (TLRs) play an integral role in activating immune pathways in response to the presence of a pathogen. Although their mechanisms of action in mediating innate immune responses are well-researched, it is still unclear whether their expression regulates adaptive immunity. Data from current literature lead to conflicting conclusions. Some studies show that TLRs, specifically TLR4, are critical to initiating adaptive immune responses, and therefore the production of antibodies, while others indicate that TLR signaling is not required. This study uses a two week prime-boost schedule of intramuscular vaccination using the model antigen ovalbumin (Ova) in wild-type (WT) and TLR4-deficient (TLR4-/-) mice. Serum ELISAs indicate that TLR4-/- mice have significantly less antibody production than WT mice after vaccination with Ova. To investigate whether the lack of TLR4 could be overcome by immunoadjuvants, mice were injected with adjuvanted Ova on days 1 and 14. The adjuvants CpG DNA (TLR9 ligand), PHAD (TLR4 ligand), and Alum (alhydrogel) are used. Serum is collected and antibody production is measured on days 14 and 28. Examining alternative pathways of stimulating adaptive immunity will potentially lead to the development of more effective vaccines, especially in immunosuppressed individuals, which will improve the health of the human population. Funding Sources Supported by Undergraduate Research Grant from Towson University’s Fisher College of Science and Mathematics Topic Categories Vaccines and Immunotherapy (VAC)