Nicotine vaccine could vanish cigarette habits in a puff of smoke

By Fiona BARRY contact

- Last updated on GMT

Puff, puff, I'll pass... a nicotine vaccine could help smokers quit. (Image: 55Laney69)
Puff, puff, I'll pass... a nicotine vaccine could help smokers quit. (Image: 55Laney69)
The Scripps Research Institute has created a nicotine conjugate vaccine with a technique it says could also treat cocaine, heroin, and methamphetamine addiction.

The vaccine stimulates the immune system to identify nicotine as a foreign antigen. This elicits antibodies that alter nicotine’s pharmacokinetics, reducing nicotine levels in the blood and ultimately entry into the central nervous system.

It consists of a large carrier protein, needed because nicotine particles alone are too small to trigger the immune system, conjugated to haptens – molecular mimics of nicotine which provoke an immune response.

The team improved on an anti-smoking vaccine trialled by Nabi BioPharmaceuticals (now Biota) that failed in Phase III clinical trials in 2011.

Nabi’s nicotine conjugate vaccine was effective only for “one-third of clinical trial participants,​” said the Scripps scientists, “likely due in part to its use of racemic nicotine hapten, (±)-3’-AmNic.​”

Scripps’s study on rats found better binding to nicotine and a greater antibody response is achieved with enantiopure (−)-3′-AmNic haptens – that is, “left-handed​” chiral​ haptens.

Our vaccine work demonstrates that careful consideration must be made in hapten design,​” co-author Jonathan Lockner told BioPharma-Reporter.com.

A previous nicotine vaccine clinical candidate may have failed partly due to the fact that it contained a mixture of “left-handed” and “right-handed” nicotine haptens.

Our improved version, which contains only “left-handed” nicotine haptens, is superior to that failed vaccine, which was a mixture. Our vaccine is better optimized for eliciting antibodies that can recognize “left-handed” nicotine molecules, which are the prevalent version of nicotine in tobacco smoke.​”

Companies taking nicotine vaccine candidates to clinical trial should incorporate these enantiopure haptens into their design, he said. “There might even be more effective haptens out there.​”

Vaccine make-up

The Scripps team created an adjuvant vaccine, using a combination of Alhydrogel (a type of alum common in vaccines) and CpG ODN (oligodeoxynucleotide), a short single-stranded DNA molecule newer to vaccine use.

CpG ODN stimulates innate immunity and stimulates B cells, monocytes, and dendritic cells. In essence, the combination of Alhydrogel and CpG ODN stimulates the immune system to respond more robustly to whatever is co-formulated with it,​” said Lockner.

The antibody therapy is a departure from small molecule-based smoking cessation methods currently on the market. These use synthetic agonists or antagonists to target brain receptors – but “do not help much​” and have side effects, said the Scripps researchers.

Lockner told us the team has “been in conversations with various suitors​” to license and commercialise the vaccine.

The research was funded by the Tobacco-Related Disease Research Program.

Source: A Conjugate Vaccine Using Enantiopure Hapten Imparts Superior Nicotine-Binding Capacity​, Journal of Medicinal Chemistry, December 10, 2014.

DOI: ​10.1021/jm501625j

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