Development and Characterization of the Immune Response Induced by Peptides and DNA Constructs that Mimic the Capsular Polysaccharide of Neisseria Meningitidis Serogroup C
Carbohydrate antigens, such as the capsular polysaccharide of Neisseria meningitidis, are considered T-independent in nature. T-independent antigens do not require T cell help to elicit an immune response and do not generate immunologic memory formation. Carbohydrate antigens have limited responses as immunogens and fail to elicit protective levels of antibodies in children less than 2 yr of age. In order to increase the immunogenicity of a capsular polysaccharide, it must be converted into a T-dependent antigen. T-dependent antigens have the ability to associate with major histocompatibility complex (MHC) molecules and be presented to T cells. This generates a memory response and overcomes the immune tolerance associated with carbohydrate antigens in the young. One method of converting a carbohydrate into a T-dependent antigen is though the use of molecular mimicry. Molecular mimicry is defined as the ability of structurally unrelated molecules to exert the same biological effect. The concept of mimicry is based on the idiotypic network that suggests mimicry is the function of reproducing the binding interaction between an antibody and antigen. Recent studies have extended this concept by demonstrating the potential of phage display libraries in selecting peptides capable of mimicking the capsular polysaccharide, and thus eliciting anti-polysaccharide antibodies when used an immunogens. A natural extension of the observation that peptides can mimic polysaccharides is the development of DNA constructs that encode peptide mimics of capsular polysaccharides. DNA constructs have been shown to induce long lasting humoral and cellular responses, and can easily be altered to manipulate the magnitude and orientation of the desired immune response. Therefore, multiple DNA encoded epitope sequences representing specific carbohydrate and protein epitopes can be included in the construct design. Therefore, DNA immunization may be useful against encapsulated organisms by directing the response to specific polysaccharide as well as protein epitopes. The following studies will describe the selection and evaluation of an immunogenic peptide mimic of N. meningitidis serogroup C capsular polysaccharide (MCPS). The studies will further describe the design of a multi-epitope DNA construct encoding a peptide mimic of MCPS, and will evaluate and characterize the anti-MCPS immune response in a murine model.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:dna vaccines capsular polysaccharide neisseria meningitidis peptide mimicry multi epitope constructs
Date of Publication:01/01/2005