UCSF has issued a
href="http://pub.ucsf.edu/newsservices/releases/200606091/">press
release describing their trial of a vaccine,
href="http://www.nabi.com/pipeline/pipeline.php?id=3" rel="tag">NicVAX®
(Nicotine Conjugate Vaccine) , for treatment of nicotine addiction.
The product is made by attaching a nicotine derivative to a
carrier protein. This is necessary because nicotine itself is
too small to elicit an immune response.
When injected, the vaccine causes the immune system to produce
antibodies that bind to nicotine. Once bound, the nicotine is
unable to cross the
href="http://en.wikipedia.org/wiki/Blood-brain_barrier">blood-brain
barrier. As a result, the smoker gets minimal
pharmacological reinforcement for the behavior. In other
words, it is not fun anymore, so it is easier to quit.
In this post, I review the status of the development of the vaccine,
say a little about how it works, and mention the two other products
currently under development.
The trial is being conducted at the
href="http://www.ucsf.edu/nosmoke/">UCSF Habit Abatement
Clinic. It is a
href="http://en.wikipedia.org/wiki/Phase_IIb#Phase_II">Phase
IIb trial, which is intended to give some preliminary
information about efficacy. The point of the trial is to
determine if further development of the product is likely to be
worthwhile. The
href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16321612">results
of the Phase I trial were encouraging, but hardly conclusive.
NicVax is one of three nicotine antibodies under development.
The others are
href="http://www.smokersvaccine.com/e/about_clinical.asp"
rel="tag">NicQb, and
href="http://www.xenova.co.uk/dc_ta_nic.html" rel="tag">TA-NIC.
NicVax is being developed by
href="http://www.nabi.com/index.php" rel="tag">Nabi
Biopharmaceuticals; NicQb by
href="http://www.cytos.com/" rel="tag">Cytos;
TA-NIC by
rel="tag">Xenova.
There is a nice summary article about the use of nicotine vaccines,
their mechanism of action, and other aspects of treatment:
LeSage MG, Keyler DE, Pentel PR.
href="http://www.aapsj.org/view.asp?art=aapsj080108#B28">Current
Status of Immunologic
Approaches to Treating Tobacco Dependence: Vaccines and
Nicotine-specific Antibodies. AAPS Journal.
2006; 8(1): E65-E75. The two most important questions
I had were addressed in this article:
In the NicVax trial, participants were neither
motivated to quit nor instructed to do so. Participants received 3
monthly vaccine injections at 1 of 3 doses followed by a booster dose
at 6 months. A greater percentage of subjects achieved 30 days of
continuous abstinence (confirmed by self-report and expired air CO) in
the high-dose vaccine group (40%) compared with the control group (8%).
There was no evidence of increased smoking according to self-report,
expired air CO, and urinary NNAL (a tobacco carcinogen nicotine
metabolite). Thus, smokers did not try to compensate for possible
reductions in nicotine distribution to brain.
The high-dose vaccine group did fairly well, but as I mentioned before,
the results are not conclusive. What is especially important
here, is that the smokers did not escalate their smoking in order to
compensate for the reduced nicotine. A major problem with
low-nicotine cigarettes is that people generally do
escalate. Even if they do not smoke more cigarettes, they
inhale more and hold the smoke longer.
I am really curious about the difference here, why smokers would
escalate in one situation, but not the other. Does anyone
have any ideas about that?
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I suspect that the carrier protein in the vaccine may kill the "need" for nicotine? Or is that way too simplistic? (Not my field by any means.) Whereas, with low tar/nicotine cigarettes, which I smoke, I orignally felt the need to drag deeper and longer as you suggest. But, I taught myself not to do that by using a super skinny cigarette and cut my smoking in half.
I really hope this vaccine works. I have tried it all.
The place looks fabulous BTW!!!
Thank you for the compliment, but I must say, this site is nowhere near as artistic as yours.
The carrier protein can't get in to the brain, so if it does anything like that, it does not do it is the brain. That makes it unlikely to be a factor (but there are a lot of strange things in this line of research, so I would not rule it out).
The only things I can think of are that the nicotine-antibody complexes might dissociate slowly, leading to a slow leaching of nicotine that gives a sort of tapering effect. But in order to know if that is even plausible, I would have to know how much nicotine gets bound, and how quickly it gets released. The other thing is that the level of antibody would increase slowly. So maybe the slow increase in antibody leads to a slow decrease in how much nicotine a person gets.
That is all speculative. Plus, the sample sizes in the early studies were small, so it really is premature to even conclude that smokers do not escalate their smoking in response to the vaccine. But it does not hurt to speculate like this.