Advancing the health and well-being of animals and people


Principal Investigator: Theodore Clark

Department of Microbiology and Immunology
Contact Information: Email: tgc3@cornell.edu; Phone: 607-253-4042
Sponsor: Texas AgriLife Research of the Texas A&M University System
Grant Number: 570757
Title: Immunostimulatory Effects of PRISM: a Novel Matrix for Production and Purification of Rapidly Deployable Vaccines
Annual Direct Cost: $191,969
Project Period: 07/01/2011-06/30/2012

DESCRIPTION (provided by applicant): The work described in this proposal will validate the immunostimulatory potential of PRISM™, a novel biological matrix for the production of multivalent vaccines for the animal industry. The PRISM™ matrix is a product of the regulated secretory pathway of Tetrahymena thermophila, a ciliated protozoan, and widely accepted model for basic research. A highly sophisticated eukaryotic cell, Tetrahymena grows rapidly (2 hr doubling time) in inexpensive media on a large scale, and is readily transformed with foreign DNA. More importantly, Tetrahymena devotes a large part of its metabolism to the production of membrane and secreted proteins that are difficult to produce in conventional microbial systems such as bacteria and yeast. Recent studies at Tetragenetics Inc have shown that viral and protozoan membrane antigens can be targeted to a pathway for regulated secretion in these cells, and can be readily harvested from culture supernatants in association with a proteinaceous gel termed PRISM™. PRISM™ offers a convenient matrix for protein purification, but has physical properties reminiscent of virus-like particles with the potential to induce potent immune responses to co-administered antigens. Moreover, PRISM™ can be engineered to incorporate protein adjuvants as well as diverse antigens targeting multiple pathogens in a single low-cost vaccine formulation. Thus PRISM TM is a rapidly deployable, crosscutting technology that may be ideal for addressing pandemic outbreaks of newly emerging zoonotic agents with importance to commercial agriculture and the U.S. government. Small-scale pilot studies in rodents have indicated that PRISM ™ can induce high-titer neutralizing antibodies against avian influenza virus using the H5 hemagglutinin as a model antigen. Here we intend to validate these preliminary findings and determine the nature of the immune response to PRISM™-based influenza vaccines in terms of antibody subtype, B- and T-cell phenotype, and long-term memory. In addition, we will provide proof-of-concept that multiple antigens and adjuvants can be incorporated into the same vaccine formulation to produce an efficient multivalent vaccine against avian influenza. This technology is applicable to a wide variety of pathogens and has the capacity to generate vaccines very rapidly in response to disease outbreaks.