Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten.
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.
Centre de Recherche Public-Santé/National Public Health Laboratory, Institute of Immunology, Luxembourg, Grand Duchy of Luxembourg.
Mario T
MT
Schellenberger
Nathalie
N
Grova
Sophie
S
Farinelle
Stéphanie
S
Willième
Dominique
D
Revets
Claude P
CP
Muller
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000493:pharmacokinetics; D004785:Environmental Pollutants / Q000276:immunology / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry*; D005260:Female; D006241:Haptens / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D004785:Environmental Pollutants; D018984:Epitopes, T-Lymphocyte; D006241:Haptens; D010455:Peptides; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D001564:Benzo(a)pyrene