Technology Developmental Project 2
Peptide Conformation Constrainment Technology & Novel Mucosal Adjuvants to Advance H. pylori Vaccine Development
Project Leader: Thomas G. Blanchard, PhD
Vaccine development for enteric pathogens has been hindered due to the difficulties in stimulating the mucosa directly through oral immunization, the lack of useful adjuvants, and difficulties in maintaining antigenic integrity within the gastrointestinal tract.
In this project we propose to use a technology that allows for construction of stable and conformationally appropriate peptide epitope motifs covalently linked to aluminum hydroxide nanoparticles. This technology could result in the production of safe and highly characterized sub-unit vaccines having the capacity to elicit immune responses against selected microbial antigens or protein active sites.
We propose to evaluate the use of this technology that involves the use of conformationally constrained synthetic H. pylori CagL peptides covalently conjugated to the calcinated aluminum hydroxide nanoparticles to be delivered orally or systemically. Our goal is to maximize targeted humoral and cellular immune responses against molecularly defined epitopes.
We will perform exploratory studies of these technologies in vitro using human and mouse cell lines, and in vivo in mice using H. pylori. The purpose of the studies will be to measure vaccine efficacy against colonization, inflammation and carcinogenesis as a precursor to studies on infected human subjects. The latter studies using human specimens will involve to determine whether there is an association of antibody levels to defined CagL epitopes with inflammation, symptomatology and disease progression (e.g., gastric cancer).