Use of Prior Vaccinations for the Development of New Vaccines

Abstract

There is currently a need for vaccine development to improve the immunogenicity of protective epitopes, which themselves are often poorly immunogenic. Although the immunogenicity of these epitopes can be enhanced by linking them to highly immunogenic carriers, such carriers derived from current vaccines have not proven to be generally effective. One reason may be related to epitope-specific suppression, in which prior vaccination with a protein can inhibit the antibody response to new epitopes linked to the protein. To circumvent such inhibition, a peptide from tetanus toxoid was identified that, when linked to a B cell epitope and injected into tetanus toxoid-primed recipients, retained sequences for carrier but not suppressor function. The antibody response to the B cell epitope was enhanced. This may be a general method for taking advantage of previous vaccinations in the development of new vaccines.

Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology

“…Regardless of the immunizing peptide, the primed LNC proliferated in response to CS.T3 378 -395 , TT 830 -855 , 1A [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] , and tetanus toxoid, but, as observed above, not in response to the presence of the two control peptides, CS.T3 scr and HP-22 (Table II). These control peptides, synthesized by the same procedures as other experimental peptides, were included as negative controls and to ensure that contaminants, if any, were not responsible for the observed cross-reactivity.…”

“…In the first instance these strains of mice were immunized with promiscuous Plasmodium falciparum peptide CS.T3 378 -395 , and the draining LNC were examined for their ability to proliferate to different peptides used in this study. Primed LNC efficiently responded to CS.T3 378 -395 , 1A [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] , TT 830 -844 peptide, and tetanus toxoid (Table II). No lymphoproliferation was observed when these LNC were stimulated with CS.T3 scr or an unrelated 22-residue peptide (HP-22) derived from a major malaria P. falciparum protein called histidine-rich protein II.…”

“…To determine whether immunization with tetanus toxoid also would induce a peptide-specific cross-reactive response, groups of two strains of mice, BALB/c and C57BL/6, were immunized with tetanus toxoid. In both strains of mice, the primed LNC proliferated significantly in response to CS.T3 378 -395 , 1A [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] , TT 830 -844 , and homologous stimulation with tetanus toxoid itself, but, once again, not when stimulated with CS.T3 scr or HP22. In all the above experiments control mice were immunized with PBS emulsified in CFA, but their LNCs gave no response to either the peptides or the protein stimulation, demonstrating and ruling out mitogenic contamination of the peptides (Table II).…”

“…A total of 5 ϫ 10 4 cells/well were cocultured with 3-5 ϫ 10 5 cells/well of irradiated (3000 rad) splenic APC from syngenic mice in RP10 medium in the presence of various concentration of peptide Ags. There were three sets of controls in the assay: 1) APC alone in medium without Ag, 2) APC plus T cells in medium without Ag, and 3) [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] 1A protein of RSV CEYNVFHNKTFELPRA PfCSP [331][332][333][334][335][336][337][338][339][340][341][342][343][344][345][346][347][348][349][350] P. falciparum CSP IEQYLKKIKNSISTEWSPCS PfCSP [345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361][362] P. falciparum CSP EWSPCSVTCGNGIQVRIK HA …”

“…Groups of mice of different strains were also immunized with either TT 830 -844 or 1A [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] , and the draining LNC were examined for their ability to proliferate in response to stimulation with the three promiscuous T cell epitopes. Regardless of the immunizing peptide, the primed LNC proliferated in response to CS.T3 378 -395 , TT 830 -855 , 1A [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] , and tetanus toxoid, but, as observed above, not in response to the presence of the two control peptides, CS.T3 scr and HP-22 (Table II).…”