Effects of Innate Immune Modulators, Vaccine Adjuvants and Vaccine Administration on Immune Response
Research Team
- Project leader: Heather Wilson
- Technician: Rachelle Buchanan
- Graduate student: Tova Dybvig
Overview
Adjuvants are vaccine components that influence the host immune response through mechanisms such as assistance in antigen delivery and presentation, promotion of cellular recruitment, promotion of inflammation to trigger a danger response in the host, and through localizing and protecting antigens. We propose that by combining adjuvants that mediate their effects via complementary mechanisms, we can produce a vaccine formulation with a strong and specific humoral and cell mediated immune response against antigens in neonates and adults.Host defense peptides (HDPs) are small, naturally occurring peptides expressed in plants, mammals, amphibians, fish, and insects and they are found at mucosal surfaces such as the skin, oral mucosa, gastrointestinal tract, etc. Most HDPs have inherent antimicrobial activity and they can influence host immune responses.
Hypomethylated CpG motifs are characteristic of bacterial, viral and protozoal DNA and their presence can influence host immune responses. As an adjuvant, co-immunization of antigens with synthetic CpG ODNs may promote a balanced Th1/Th2 immune response which is desirable in many vaccine formulations and especially for neonatal vaccines.
Polyphosphazenes (PP) are high-molecular weight, water-soluble polymers that localize and stabilize antigens resulting in increased efficiency of presentation to immune cells.
In this research project, we use a combination of adjuvants known to mediate their effects through distinct mechanism in the presence of pertussis toxoid to further clarify the effect adjuvants influence on antigen migration, and to assess whether retention at the site of injection correlates with a favorable immune response. The characterization of the immune response is being established through kinetics response analysis, isotype profiling, analysis of cytokine secretion and histological assessment of cell recruitment on the site of infection.
Objectives:
- Establish how the route of vaccine administration and vaccine formulation influences the host immune response.
- Establish whether antigen retention at site of administration correlates with immunogenicity. Establish the cell signaling events through which HDPs and CpG ODNs mediate their immune modulatory effects.
- Establish whether HDPs can act as an alternative to antibiotics.
Future Direction and Vision
We have identified several pathways in bovine and porcine immune cells that are influenced by HDPs, CpG ODN, PP and PP-based microparticles. We intend to determine if vaccine efficacy can be predicted by vaccine formulation and administration.
