Helix Stabilization in the C-Terminal Peptide of Chicken Riboflavin Carrier Protein Enhances Immunogenicity and Prolongs Contraceptive Potential as an Epitope-Based Vaccine in Female Rats

Sarada, Subramanian and Karande, Anjali A and Adiga, Radhakantha P (2001) Helix Stabilization in the C-Terminal Peptide of Chicken Riboflavin Carrier Protein Enhances Immunogenicity and Prolongs Contraceptive Potential as an Epitope-Based Vaccine in Female Rats. In: Biochemical and Biophysical Research Communications, 287 (1). pp. 236-243.

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Abstract

Earlier investigations have shown that (a) antibodies against a carrier-coupled 20-residue synthetic peptide (C-20), $^{200}HACQKKLLKFEALQQEEGEE^{219}$, corresponding to the C-terminal partially helical sequence of chicken riboflavin carrier protein (RCP; 219 AA) curtail pregnancy in mammals and (b) helix stabilization by introducing appropriately spaced salt bridges in the flanking sequences of its B-cell epitopic structure enhances RCP antigenicity to peptide antibodies. Among such engineered C-20 analogs, HE-20 (HAEQKKLLKFEALEQEKGKE) exhibited maximum helical propensity. Since C-20 per se, i.e., without carrier conjugation, elicits RCP-reactive neutralizing antibodies in rodents, we mapped its T-cell epitope which overlaps its B-cell epitope, both of which remain unmodified in HE-20. Comparative evaluation of immunogenicity of the two epitope-based peptide vaccines showed that HE-20 was far superior to C-20 in generating RCP-reactive antibodies in terms of both affinity and titer. With regard to bioefficacy, passive immunoneutralization of RCP in pregnant rats by administering purified IgG from either of the antipeptide sera terminated pregnancy. Similarly, active immunization of fertile female rats with the individual peptide analogs curtailed pregnancy. However, HE-20 was more efficient in eliciting higher affinity, longer-lasting, RCP-crossreactive antibodies with consequently more prolonged immunocontraceptive efficacy.

Item Type:	Journal Article
Publication:	Biochemical and Biophysical Research Communications
Publisher:	Elsevier Science
Additional Information:	The copyright of this article belongs to Elsevier Science.
Keywords:	Antigenicity;contraception;helix stabilization; immunogenicity;riboflavin carrier protein;synthetic peptides.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	01 Oct 2007
Last Modified:	01 Mar 2012 06:52
URI:	http://eprints.iisc.ac.in/id/eprint/11991

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