How well can an idiotope peptide mimic replace its parent idiotype in a synthetic peptide vaccine?
OBJECTIVE
To determine whether a vaccine consisting of an idiotope peptide mimic of the third complementarity-determining region of the immunoglobulin heavy chain (CDR-H3) is an effective substitute for its parent idiotype. Such peptide vaccines could ultimately be used for targeting pathological B lymphocytes.


METHODS
Hen egg lysozyme (HEL) conjugates of the Fab' fragment of monoclonal anti-fluorescein antibody 9-40 (Fab'-HEL) or a peptide mimic of the 9-40 CDR-H3 (referred to as the "B epitope" or "Bep," the conjugate is referred to as "Bep-HEL") were injected into separate cohorts of B10.A mice. Two additional control cohorts were injected with either the Bep peptide alone or a noncovalent mixture of Bep and HEL. Sera were assayed for both anti-idiotope and anti-idiotype activity by enzyme-linked immunosorbant assay (ELISA). Primary, secondary, and tertiary immune responses were examined.


RESULTS
Both the Bep-HEL idiotope and the Fab-HEL idiotype immunogens elicited homologous, allogenic immune responses. No cross-reactivity was observed between anti-idiotope and anti-idiotype responses after primary immunization. With secondary immunization, 50% of mice immunized with the Bep-HEL conjugate exhibited a cross-reactive anti-idiotype response. Conversely, 100% of mice immunized with the Fab'-HEL conjugate exhibited a marginal, but statistically significant cross-reactive anti-idiotope response. Upon tertiary immunization, 100% of mice immunized with Bep-HEL exhibited a cross-reactive anti-idiotype response, and 55.6% of mice immunized with the Fab'-HEL conjugate exhibited a cross-reactive anti-idiotope response.


CONCLUSIONS
Covalent coupling of a xenogenic carrier protein to an idiotype immunogen or its peptide mimic significantly enhances the intensity of homologous, allogenic anti-idiotype or anti-idiotope immune responses. Multiple immunizations are necessary to induce cross-reactivity between the peptide mimic and its parent idiotype.
Cavenaugh
James S
JS
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Wang
Hsu-kun
HK
Sha
Jiang
J
Hansen
Corey
C
Papangkorn
Kongnara
K
Smith
Richard S
RS
Herron
James N
JN
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D022801:Complementarity Determining Regions / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009113:Muramidase / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D014612:Vaccines / Q000138:chemical synthesis / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D022801:Complementarity Determining Regions; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D010455:Peptides; D014612:Vaccines; C421864:hen egg lysozyme; D009113:Muramidase