Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid A.
We have investigated the parameters affecting the immunogenicity of a short synthetic hexapeptide associated with liposomes. The model peptide used had the sequence IRGERA which corresponds to the C-terminal hexapeptide region of histone H3. Immunogenicity was measured by the ability of anti-peptide antibodies to cross-react with the parent protein. By itself, the peptide was not able to induce significant antibody production. However, liposomes were shown to be able to render the peptide immunogenic, nevertheless a number of parameters were important: to be immunogenic the peptide had to be surface bound, rather than entrapped within the liposomes, and an adjuvant, monophosphoryl lipid A (MPLA), had to be present in the same population of liposomes. Additionally, the intensity and duration of the immune response were found to be dependent both on the charge of the liposomes; neutral liposomes yielding a longer lasting response than negatively charged liposomes, and on the immunisation schedule where a long time period between immunisation and boosting yielded a better result than a short time period. To account for these phenomena we propose a model in which surface-bound antigen targets liposomal MPLA to B lymphocytes specific for the antigen. These results demonstrate that liposomes containing the non-toxic adjuvant MPLA can act as carriers to induce a long-lasting IgG response against peptides, eliminating the need of protein carriers and conventional adjuvants. Such an approach may be useful for designing synthetic vaccines.
Friede
M
M
Laboratoire de Chimie Bioorganique (CNRS URA 1386), Université Louis Pasteur, Illkirch, France.
Muller
S
S
Briand
J P
JP
Van Regenmortel
M H
MH
Schuber
F
F
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005612:Freeze Drying; D006657:Histones / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D013010:Sonication; D014611:Vaccination
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D006657:Histones; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D008081:Liposomes; D010446:Peptide Fragments; C048436:monophosphoryl lipid A