Construction of an enantiopure bivalent nicotine vaccine using synthetic peptides

Abstract

Clinical outcomes of anti-nicotine vaccines may be improved through enhancements in serum antibody affinity and concentration. Two strategies were explored to improve vaccine efficacy in outbred mice: the use of enantiopure haptens and formulation of a bivalent vaccine. Vaccines incorporating natural (-) nicotine haptens improved relative antibody affinities >10-fold over (+) haptens, stimulated a two-fold boost in nicotine serum binding capacity, and following injection with 3 cigarette equivalents of nicotine, prevented a larger proportion of nicotine (>85%) from reaching the brain. The activity of a bivalent vaccine containing (-) 3’AmNic and (-) 1’SNic haptens was then compared to dose-matched monovalent groups. It was confirmed that antisera generated by these structurally distinct haptens have minimal cross-reactivity and stimulate different B cell populations. Equivalent antibody affinities were detected between the three groups, but the bivalent group showed two-fold higher titers and an additive increase in nicotine serum binding capacity as compared to the monovalent groups. Mice immunized with the bivalent formulation also performed better in a nicotine challenge experiment, and prevented >85% of a nicotine dose equivalent to 12 cigarettes from reaching the brain. Overall, enantiopure conjugate vaccines appear to improve serum antibody affinity, while multivalent formulations increase total antibody concentration. These findings may help improve the performance of future clinical candidate vaccines.

Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine

“…Current parenteral and mucosal nicotine vaccines have been published with varying degrees of efficacy [13][14][15][16][17][18][30][31][32] and they all demonstrate significant levels of anti-nicotine antibodies that are able to block nicotine from entering the brain. Despite this similarity, the challenge and nicotine analysis methods vary and nicotine recovery tends to be low.…”

“…While effective, recently there has been a shift away from using [ 3 H]-nicotine for nicotine challenges, and towards using nicotine tartrate to assess the distribution of nicotine by GC/MS, LC/MS or HPLC. However, unlike [ 3 H]-nicotine, that is typically if not always delivered intravenously (IV), non-tritiated forms of nicotine have been delivered subcutaneously (SC) [13][14][15][16], IV [17], or intraperitoneally (IP) [18], all of which resulted in low levels of recovery, regardless of the dose administered. This does not necessarily permit nicotine vaccines evaluated in vivo to be properly assessed due to the low recovery rates in the brain and the sera.…”

Smoking Cessation Treatments: Current Psychological and Pharmacological Options

“…It would be indicated for the following groups of subjects: (a) heavy smokers who have made multiple unsuccessful attempts to quit using different methods; (b) patients who are highly motivated to quit; and (c) patients who have positive attitudes toward vaccines 20 . Modifications designed to improve serum antibody affinity are being tested and may improve the performance of future clinical candidate vaccines [21][22][23] .…”

Epitope targeting with self-assembled peptide vaccines

“…9–12 We have used this carrier to produce a nicotine vaccine for smoking cessation and have shown that the Ab concentrations induced in mice and rats can bind supraphysiological doses of nicotine and prevent nicotine-induced toxicity. 8,13,14…”