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

PLoS One. 2012;7(5):e38329. doi: 10.1371/journal.pone.0038329. Epub 2012 May 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology*
  • Antibody Specificity*
  • Benzo(a)pyrene / metabolism*
  • Benzo(a)pyrene / pharmacokinetics
  • Environmental Pollutants / immunology
  • Environmental Pollutants / pharmacokinetics
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / chemistry*
  • Female
  • Haptens / immunology*
  • Immunization
  • Mice
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism*
  • Tetanus Toxoid / immunology
  • Time Factors
  • Vaccines, Conjugate / immunology*
  • Vaccines, Conjugate / metabolism

Substances

  • Antibodies
  • Environmental Pollutants
  • Epitopes, T-Lymphocyte
  • Haptens
  • Peptides
  • Tetanus Toxoid
  • Vaccines, Conjugate
  • Benzo(a)pyrene