Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten

• Published in: PloS one 2012-05, Vol.7 (5), p.e38329
• Main Authors: Schellenberger, Mario T, Grova, Nathalie, Farinelle, Sophie, Willième, Stéphanie, Revets, Dominique, Muller, Claude P
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies - immunology; Antibody response; Antibody Specificity; Antigenic determinants; Antigens; Aromatic hydrocarbons; Benzo(a)pyrene; Benzo(a)pyrene - metabolism; Benzo(a)pyrene - pharmacokinetics; Benzopyrene; Biology; Blood; Carcinogens; Carriers; Chemistry; Conjugates; Contaminants; Deoxyribonucleic acid; Diphtheria; DNA; Effectiveness; Environmental Pollutants - immunology; Environmental Pollutants - pharmacokinetics; Enzyme-Linked Immunosorbent Assay; Enzymes; Epidemiology; Epitopes; Epitopes, T-Lymphocyte - chemistry; Excretion; Female; Food contamination; Food contamination & poisoning; Haemophilus influenzae; Haptens - immunology; Immunity; Immunization; Immunogenicity; Immunoglobulins; Immunology; Laboratories; Lymphocytes; Lymphocytes T; Measles; Medicine; Metabolism; Metabolites; Mice; Molecular Sequence Data; Molecular weight; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Pollutants; Polycyclic aromatic hydrocarbons; Proteins; Public health; Pyrene; Selectivity; Studies; T cells; Tetanus; Tetanus toxin; Tetanus Toxoid - immunology; Time Factors; Toxins; Tumors; Vaccination; Vaccines; Vaccines, Conjugate - immunology; Vaccines, Conjugate - metabolism; Whooping cough
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038329

The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted.