Journal Article

Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier

Miller, Keith D., Roque, Richard, Clegg, Christopher H.

2014

Overview

Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH), we have synthesized a short trimeric coiled-coil peptide (TCC) that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg) from reaching the brain.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adjuvants, Immunologic - pharmacology / Alum / Aluminum sulfate / Analysis / Animal models / Animals / Antibodies / Antibodies - blood / Antibodies - immunology / Antibody Affinity - immunology / Antigenic determinants / Antigens / Binding / Biology and Life Sciences / Brain / Brain - metabolism / Cancer / Cardiovascular diseases / Carriers / Cigarette smoking / Cigarettes / Coronary artery disease / Cytomegalovirus / Density / Drug addiction / Drug dosages / Epitopes / Female / Haptens - immunology / Health aspects / Health problems / Heart diseases / Immune response / Immune system / Immunogenicity / Immunoglobulins / Laboratory animals / Lymphocytes / Lymphocytes B / Lymphocytes T / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Nicotine / Nicotine - immunology / Peptides / Peptides - immunology / Proteins / Public health / Smoking / Smoking cessation / Smoking Cessation - methods / Software packages / Stoichiometry / T cells / Tetanus / TLR4 protein / Tobacco / Tobacco Use Disorder - therapy / Toll-Like Receptor 4 - agonists / Toll-like receptors / Vaccines / Vaccines, Synthetic - immunology