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 preexisting 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.