Synthetic peptide representing a T-cell epitope of CRM197 substitutes as carrier molecule in a Haemophilus influenzae type B (Hib) conjugate vaccine.
The cross-reactive material (CRM197) of diphtheria toxin is considered to be advantageous as a carrier molecule in the formulation of a Haemophilus influenzae type b conjugate vaccine. In order to more precisely understand the function of the CRM197 in the vaccine, we have begun mapping the T-cell epitopes of the protein. A peptide which represents a segment of the primary sequence of CRM197 has been identified and found to stimulate diphtheria toxoid or CRM197-primed murine T-lymphocytes. In addition, the peptide is capable of priming T-cells in vivo for a subsequent in vitro T-cell response to itself or to the intact CRM197 molecule. The ability of the peptide to replace CRM197 as a carrier molecule was examined by immunizing mice with PRP, PRP-CRM197 conjugate, or PRP covalently coupled to the peptide. Antibodies to PRP were only detected in the PRP-CRM197 or PRP-peptide immunized groups. Both conjugates elicited primary and secondary antibody responses. Thus, a synthetic peptide representing a defined T-cell epitope of CRM197 has been functionally demonstrated based on its ability to act as a carrier molecule in a PRP conjugate vaccine.
Bixler
G S
GS
Praxis Biologics, Inc., Rochester, NY 14623.
Eby
R
R
Dermody
K M
KM
Woods
R M
RM
Seid
R C
RC
Pillai
S
S
D000818:Animals; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D008213:Lymphocyte Activation; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011135:Polysaccharides, Bacterial; D013601:T-Lymphocytes / Q000276:immunology*
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D000939:Epitopes; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D010455:Peptides; D011135:Polysaccharides, Bacterial; C028581:CRM197 (non-toxic variant of diphtheria toxin)