Liposome-entrapped T-cell peptide provides help for a co-entrapped B-cell peptide to overcome genetic restriction in mice and induce immunological memory.
We have investigated the possibility of a T-cell epitope peptide providing help for a B-cell epitope peptide when both peptides are co-entrapped in the same liposomes. Epitope models used were a 28 amino acid peptide from the S region of the hepatitis B surface antigen (HBsAg) (subtype adw) containing an H-2s Th-cell epitope, and a 33 amino acid peptide from the pre-S1 region of the HBsAg (subtype adw) designed to exclude an adjacent H-2s T-cell epitope, the latter (pre-S1) peptide being recognized by SJL (H-2s) mice as a B-cell epitope. SJL(H-2s) mice were immunized twice intramuscularly with S or pre-S1 peptide alone, co-entrapped in the same liposomes or entrapped in separate liposomes which were mixed before injection. Analysis of sera for anti-peptide IgG1 antibodies revealed that the Th-cell peptide provided help for the pre-S1 peptide only when the two peptides were co-entrapped in the same vesicles. This helper effect was found to correlate with the ability of S peptide (co-entrapped with the pre-S1) to stimulate T-cell proliferation in vitro. There was no IgG1 response against pre-S1 peptide in mice immunized with a mixture of the free peptides or a mixture of separately entrapped peptides. A helper effect, albeit much weaker, was also observed in mice immunized with the two peptides emulsified in incomplete Freund's adjuvant. Antisera from mice immunized with both peptides co-entrapped in liposomes were found to bind to full length (pre-S1 containing) recombinant HBsAg. Moreover, binding values were much higher than those seen with antisera from animals immunized with the liposomal S peptide above, presumably because of full access of anti-pre-S1 antibodies to the pre-S1 region of the rHBsAg. It is concluded that liposomes could serve not only as an immunological adjuvant for peptides but also as a carrier for Th- and B-cell epitopes thus eliminating the need for covalent linkage to a carrier protein.
Gregoriadis
G
G
Centre for Drug Delivery Research, School of Pharmacy, University of London, U.K.
Wang
Z
Z
Barenholz
Y
Y
Francis
M J
MJ
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology*; D008081:Liposomes / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000939:Epitopes; D007074:Immunoglobulin G; D008081:Liposomes; D010455:Peptides; D011994:Recombinant Proteins