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
S. Subramanian et al., 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, BIOC BIOP R, 287(1), 2001, pp. 236-243
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Earlier investigations have shown that (a) antibodies against a carrier-cou
pled 20-residue synthetic peptide (C-20), (200)HACQKKLLKFEALQQEEGEE(219), c
orresponding to the C-terminal partially helical sequence of chicken ribofl
avin carrier protein (RCP; 219 AA) curtail pregnancy in mammals and (b) hel
ix stabilization by introducing appropriately spaced salt bridges in the fl
anking sequences of its B-cell epitopic structure enhances RCP antigenicity
to peptide antibodies. Among such engineered C-20 analogs, HE-20 (HAEQKKLL
KFEALEQEKGKE) 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 immun
ogenicity of the two epitope-based peptide vaccines showed that HE-20 was f
ar superior to C-20 in generating RCP-reactive antibodies in terms of both
affinity and titer. With regard to bioefficacy, passive immunoneutralizatio
n of RCP in pregnant rats by administering purified IgG from either of the
antipeptide sera terminated pregnancy. Similarly, active immunization of fe
rtile female rats with the individual peptide analogs curtailed pregnancy.
However, HE-20 was more efficient in eliciting higher affinity, longer-last
ing, RCP-crossreactive antibodies with consequently more prolonged immunoco
ntraceptive efficacy. (C) 2001 Academic Press.