NicVAX
Encyclopedia
NicVAX is a nicotine
conjugate vaccine
intended to reduce or eliminate physical addiction to nicotine
. According to the U.S. National Institute on Drug Abuse, NicVAX can potentially be used to inoculate
against addiction. This proprietary vaccine is being developed by Nabi Biopharmaceuticals of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten
3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa
exoprotein A.
Nicotine is a small molecule
that upon inhalation into the lungs quickly passes into the bloodstream and subsequently reaches the brain by crossing the blood-brain barrier
. Once in the brain, the nicotine binds to specific nicotine receptors resulting in the release of stimulants, such as dopamine
, a chemical linked to pleasure and to addiction.
NicVAX is designed to stimulate the immune system
to produce antibodies that bind to nicotine in the bloodstream and prevent it from crossing the blood-brain barrier and entering the brain. With a reduced amount of nicotine reaching the brain, fewer stimulants are released and the pleasurable, positive-reinforcing effects of nicotine are diminished, thereby making it easier to quit smoking. Pre-clinical studies with NicVAX have shown that vaccination prevents nicotine from reaching the brain and blocks the effects of nicotine, including effects that can lead to addiction
or can reinforce and maintain addiction, in animals. NicVAX, in combination with quit-counseling, has been clinically demonstrated in smokers, who sincerely want to quit, having a better chance of breaking their smoking addiction.
NicVAX is still under development; a phase IIB proof-of-concept study was completed in November 2007. Nabi issued a press release in November 2007 indicating that phase IIB testing was a success, showing statistically significant rates of smoking cessation
and continuous long-term smoking abstinence during the trial period.
Nabi Biopharmaceuticals initiated two Phase III trials of NicVAX. The first trial started in November 2009 and the second in March 2010. Nabi issued press releases announcing the start of these trials. The trials are being conducted in locations throughout the United States.
into the arm; the 3'-aminomethylnicotine molecule found in the vaccine instigates an immune response in which 'nicotine' antibodies are created. The antibodies bind to nicotine molecules, causing the merged molecules to be too large to enter the brain; this prevents nicotine from being able to affect the body. The idea behind the drug is that since often even a single cigarette can deliver enough nicotine to the brain to reinstate the addiction, blocking the entry of nicotine into the brain might prevent this renewed dependence. This treatment works for nicotine addiction from any source. Clinical Pharmacology & Therapeutics considers this method "attractive," since the antibody does not enter the brain; as a result, side effects on the central nervous system
are not expected. Additionally, the antibodies produced bond only with nicotine.
However, while this drug may curtail addiction, it does not prevent psychological cravings; in fact, a user could potentially smoke heavily to compensate for the nullifying effects of NicVAX. However, a study performed indicated that this did not happen among the test subjects.
A study performed in 2005 for 38 weeks by the University of Minnesota Cancer Center's Transdisciplinary Tobacco Use Research Center and published in Clinical Pharmacology & Therapeutics, involved 68 smokers, none of whom had known health problems or intended to quit smoking in the next month. Subjects were not instructed to quit smoking during the course of the study. The test subjects were injected four times throughout the trial: when it began, and after four, eight and 26 weeks with either one of three dosages of NicVAX or a placebo
. At the conclusion of the study, it was concluded that NicVAX was "safe and well-tolerated", with side effects including headache
s, colds
, and upper respiratory tract
infections. While most of the test subjects continued to smoke, six people from the high dosage group, one person from the medium dosage group, no one from the low dosage group, and two people from the placebo group quit smoking. They did not start again for at least thirty days.
In the Phase IIb trial, a statistically significant number of patients with a high anti-nicotine antibody
response met the primary endpoint of eight weeks of continuous abstinence between weeks 19-26. The top 30% of antibody responders (61 of the total 201 patients receiving drug) were examined in detail. A statistically significant number of these patients, (24.6%; p=0.04) showed continuous abstinence between weeks 19-26 compared to only 13.0% for the 100 patients receiving placebo. The quit rate of those patients who did not have a high antibody response was not statistically significant from placebo. The trial enrolled a total of 301 heavy smokers who smoked an average of 24 cigarettes per day prior to enrollment.
In July 2011 the first of two planned phase III trials for NicVAX failed http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=1586001&highlight=, sending the market capitalization of NABI Biopharmaceuticals to below the value of its cash holdings.
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
conjugate vaccine
Conjugate vaccine
A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein , thereby conferring the immunological attributes of the carrier on the attached antigen...
intended to reduce or eliminate physical addiction to nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
. According to the U.S. National Institute on Drug Abuse, NicVAX can potentially be used to inoculate
Inoculation
Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a human or animal, especially to produce or boost immunity to a specific disease...
against addiction. This proprietary vaccine is being developed by Nabi Biopharmaceuticals of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten
Hapten
A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself...
3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
exoprotein A.
Nicotine is a small molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
that upon inhalation into the lungs quickly passes into the bloodstream and subsequently reaches the brain by crossing the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. Once in the brain, the nicotine binds to specific nicotine receptors resulting in the release of stimulants, such as dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, a chemical linked to pleasure and to addiction.
NicVAX is designed to stimulate the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to produce antibodies that bind to nicotine in the bloodstream and prevent it from crossing the blood-brain barrier and entering the brain. With a reduced amount of nicotine reaching the brain, fewer stimulants are released and the pleasurable, positive-reinforcing effects of nicotine are diminished, thereby making it easier to quit smoking. Pre-clinical studies with NicVAX have shown that vaccination prevents nicotine from reaching the brain and blocks the effects of nicotine, including effects that can lead to addiction
Addiction
Historically, addiction has been defined as physical and psychological dependence on psychoactive substances which cross the blood-brain barrier once ingested, temporarily altering the chemical milieu of the brain.Addiction can also be viewed as a continued involvement with a substance or activity...
or can reinforce and maintain addiction, in animals. NicVAX, in combination with quit-counseling, has been clinically demonstrated in smokers, who sincerely want to quit, having a better chance of breaking their smoking addiction.
NicVAX is still under development; a phase IIB proof-of-concept study was completed in November 2007. Nabi issued a press release in November 2007 indicating that phase IIB testing was a success, showing statistically significant rates of smoking cessation
Smoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
and continuous long-term smoking abstinence during the trial period.
Nabi Biopharmaceuticals initiated two Phase III trials of NicVAX. The first trial started in November 2009 and the second in March 2010. Nabi issued press releases announcing the start of these trials. The trials are being conducted in locations throughout the United States.
Administration and effects
NicVAX is administered via an injectionInjection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
into the arm; the 3'-aminomethylnicotine molecule found in the vaccine instigates an immune response in which 'nicotine' antibodies are created. The antibodies bind to nicotine molecules, causing the merged molecules to be too large to enter the brain; this prevents nicotine from being able to affect the body. The idea behind the drug is that since often even a single cigarette can deliver enough nicotine to the brain to reinstate the addiction, blocking the entry of nicotine into the brain might prevent this renewed dependence. This treatment works for nicotine addiction from any source. Clinical Pharmacology & Therapeutics considers this method "attractive," since the antibody does not enter the brain; as a result, side effects on the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
are not expected. Additionally, the antibodies produced bond only with nicotine.
However, while this drug may curtail addiction, it does not prevent psychological cravings; in fact, a user could potentially smoke heavily to compensate for the nullifying effects of NicVAX. However, a study performed indicated that this did not happen among the test subjects.
Studies
Initial tests, involving injections of nicotine-specific immunoglobulin G into laboratory rats in the early 2000s, resulted in nicotine levels in the brain cut by up to 65%.A study performed in 2005 for 38 weeks by the University of Minnesota Cancer Center's Transdisciplinary Tobacco Use Research Center and published in Clinical Pharmacology & Therapeutics, involved 68 smokers, none of whom had known health problems or intended to quit smoking in the next month. Subjects were not instructed to quit smoking during the course of the study. The test subjects were injected four times throughout the trial: when it began, and after four, eight and 26 weeks with either one of three dosages of NicVAX or a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. At the conclusion of the study, it was concluded that NicVAX was "safe and well-tolerated", with side effects including headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, colds
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
, and upper respiratory tract
Upper respiratory tract
The upper respiratory tract or upper airway primarily refers to the parts of the respiratory system lying outside of the thorax or above the sternal angle. Another definition commomly used in medicine is the airway above the glottis or vocal cords...
infections. While most of the test subjects continued to smoke, six people from the high dosage group, one person from the medium dosage group, no one from the low dosage group, and two people from the placebo group quit smoking. They did not start again for at least thirty days.
In the Phase IIb trial, a statistically significant number of patients with a high anti-nicotine antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response met the primary endpoint of eight weeks of continuous abstinence between weeks 19-26. The top 30% of antibody responders (61 of the total 201 patients receiving drug) were examined in detail. A statistically significant number of these patients, (24.6%; p=0.04) showed continuous abstinence between weeks 19-26 compared to only 13.0% for the 100 patients receiving placebo. The quit rate of those patients who did not have a high antibody response was not statistically significant from placebo. The trial enrolled a total of 301 heavy smokers who smoked an average of 24 cigarettes per day prior to enrollment.
In July 2011 the first of two planned phase III trials for NicVAX failed http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=1586001&highlight=, sending the market capitalization of NABI Biopharmaceuticals to below the value of its cash holdings.