THE CHARACTERIZATION OF ANTIBODIES FROM SUBJECTS VACCINATED WITH NICVAXᵀᴹ

Abstract

Nicotine, which is found in tobacco, is highly addictive causing over 1 billion people worldwide to use tobacco products and causing approximately 5 million premature, preventable deaths each year. Our long term goal is to produce a nicotine vaccine which will be efficacious in preventing and treating the addiction to smoking. The nicotine vaccine produced by Nabi Biopharmaceuticals known as NicVAXNicotine, which is found in tobacco, is highly addictive causing over 1 billion people worldwide to use tobacco products and causing approximately 5 million premature, preventable deaths each year. Our long term goal is to produce a nicotine vaccine which will be efficacious in preventing and treating the addiction to smoking. The nicotine vaccine produced by Nabi Biopharaceuticals known as NicVAXᵀᴹ is a conjugate vaccine consisting of trans-3'aminomethylnicotine (a nicotine derivative) conjugated to recombinant Pseudomonas aeruginosa exoprotein A (rEPA). Animal studies have shown that nicotine antibodies reduce the amount of nicotine in the brain and increase the amount of nicotine in the blood serum significantly after animals have been given nicotine in a quantity and delivery to mimic smoking in humans. It is well established that immunogenicity, affinity and specificity all play a role in the efficacy of vaccines. To date in human subjects receiving the vaccine, significant antibody levels are induced, becoming higher when higher amounts of NicVAX are given. The antibody specificity is similar to that found in animal studies. The antibody affinity in samples from human subjects has not been studied. The connection between affinity and efficacy will be important for further development of the vaccine. We hypothesize that people with the highest affinity antibodies will have a significantly larger percentage of people able to quit smoking for one year from the time of the first vaccination. Competitive radioimmunoassay (RIA) has been used to study the affinity in samples from animal studies; however with the number of samples potentially available from this study using a more automated method such as surface plasmon resonance (SPR) will be needed. The experimental focus of this proposal is to determine whether SPR can be used to determine the affinity of antibodies for nicotine in human serum samples, to make these determinations and correlate these results with efficacy measurements. The specific aims are: 1. Correlate the affinity measurement using competitive radioimmunoassay (RIA) with surface plasmon resonance (SPR) results. (i) Test a selection of samples using RIA and then (ii) determine the best method for SPR using these samples. 2. Determine affinity of serum samples containing significant levels of nicotine specific antibody and correlate with smoking cessation and the amount of NicVAX the patient receives.