Date Published: May 30, 2012
Publisher: Public Library of Science
Author(s): Mario T. Schellenberger, Nathalie Grova, Sophie Farinelle, Stéphanie Willième, Dominique Revets, Claude P. Muller, Sylvie Alonso. http://doi.org/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.
Benzo[a]pyrene (B[a]P) is a ubiquitous environmental pollutant and food contaminant belonging to the group of polycyclic aromatic hydrocarbons (PAH). B[a]P is produced during incomplete combustion of organic matter and emanates from natural and anthropogenic sources including industrial processes, cooking, barbequing and tobacco consumption . Uptake in humans is mostly by inhalation of contaminated air, cigarette smoke and ingestion of contaminated food or water. As a consequence exposure to B[a]P by the general public is unavoidable.
In our previous work we showed that the conjugation of B[a]P-BA to TT or diphtheria toxoid (DT) induces high titers of B[a]P-specific antibodies . Here we demonstrate that similar or even better B[a]P-specific antibody titers can be induced by reducing the carrier size to a single promiscuous TCE.