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Scripps Scientists Discover New Vaccine To Help Smokers Quit

A cigarette box with the Surgeon General's Warning is shown.
Debora Cartagena, CDC
A cigarette box with the Surgeon General's Warning is shown.
Scripps Scientists Discover New Vaccine To Help Smokers Quit
Scripps Scientists Discover New Vaccine To Help Smokers Quit GUESTS:Jonathan Lockner, PhD is a research associate at The Scripps Research Institute and first author of a new paper on a nicotine vaccine.Thomas Novotny MD, is professor and co-director of the Joint Degree Program in Global Health at San Diego State University and former assistant surgeon general.

Maureen Cavanaugh: This is KPBS Midday Edition, I am Maureen Cavanaugh. Beating an addiction to cigarettes is tough. Ask any smoker or any former smoker how often they tried to quit. Science is making efforts to help a few years ago of vaccine aimed at blunting the effects of nicotine in the brain was introduced but it was found not to work for most smokers in clinical trials. So scientists at Scripps Research Institute have taken a second look at that vaccine and have found with a few structural changes it could work much better. Joining me to talk about the new research and about the effectiveness of the current dates to quit smoking are my guests Jonathan Lockner who’s Research Associate at Scripps Research Institute and first author of a new paper on a nicotine vaccine. Jonathan welcome to the program. Jonathan Lockner: Thank you for having me. Maureen Cavanaugh: Dr. Thomas Novotny, who’s Professor and Co-Director of the Joint Degree Program in Global Health at San Diego State University. He is a former assistant US Surgeon General. Dr. Nuvotny, welcome back. Dr. Thomas Novotny: Thanks. Nice to be here again, Maureen. Maureen Cavanaugh: Now, Jonathan, give us an overview. What is a nicotine vaccine supposed to do? Jonathan Lockner: Okay, let’s first start with nicotine itself. When a smoker inhales smoke the nicotine travels into the lungs, is absorbed, passes into the bloodstream and then within 10 to 20 seconds it arrives in the brain and passes the blood brain barrier and hits the receptors in the brain involved in the dopamine reward response and that perpetuates tobacco use. Maureen Cavanaugh: You want to do it again? Jonathan Lockner: Yes. And so the idea with the vaccine is that we leverage the body’s own immune system to produce antibodies that circulate in the bloodstream that then are present the next time that nicotine is present in the bloodstream. And those antibodies bind to the nicotine and prevent the nicotine from passing into the brain. Maureen Cavanaugh: So, Dr. Novotny that the concept seems to be that if a vaccinated person smoked a cigarette they would feel no effects of nicotine? Dr. Thomas Novotny: Well they would feel less effects, I mean it depends on if the vaccine is 100 % effective or not, but nicotine is the culprit in keeping people smoking and creating this widespread epidemic of smoking that persists. We haven’t overcome the addiction in a way that actually works in the treatment for it is still imperfect, that’s for sure. Maureen Cavanaugh: Jonathan, the nicotine vaccine developed a few years ago only proved effective for about 30% of the smokers in clinical trials and what you found is that it had something to do with the structure of the nicotine molecule. In layman’s terms, can you explain to us what you found? Jonathan Lockner: I will try Maureen. Maureen Cavanaugh: Okay. Jonathan Lockner: So, nicotine and most naturally occurring molecules have chirality. Chirality is a fancy term for handedness. So you have a left hand and a right hand. They are very similar, the both hands, but they are non-superimposable. And so it turns out that nicotine in tobacco smoke is by and large left-handed so to speak. And so the nicotine vaccine that was in clinical trials that failed a few years ago, as we understand it produced antibodies against both left-handed and right-handed forms of nicotine, but if the only target that we should target is the left-handed form then we should produce a vaccine that focuses like a laser on that left-handed form. Maureen Cavanaugh: Okay. So do you have these two forms of nicotine, left-handed is more prevalent in cigarettes when people try them, so the idea is that a new vaccine might be able to actually bind more of the nicotine and stop it reaching the brain. Is that it? Jonathan Lockner: Yes, because it’s optimized for the left-handed nicotine. Maureen Cavanaugh: So Jonathan, who would a vaccine like this be right for? Jonathan Lockner: I think first and foremost it’s for current users who are motivated to quit and who realized the health consequences to themselves and to their loved ones and maybe have tried other methods. We believe that this is an additional method that should be made available that leveraging the immune system is just another tactic that we can bring to bear on the nicotine addiction problem. Maureen Cavanaugh: Dr. Novotny, isn’t one of the drawbacks though that it wouldn’t help with withdrawal symptoms? Dr. Thomas Novotny: Well, they would withdraw as the nicotine is withdrawn from them, I mean there are significant symptoms, but if a smoker is motivated to quit most of the time smokers quit on their own that is without the assistance of other medications or anything, but for some smokers they need a little boost. So you know yes there’s going to be withdrawal but when they have this assistance in terms of blocking the effects of nicotine, it’s perhaps going to be more gradual and perhaps more acceptable and perhaps the rate of cessation with this assistance will be better than the 20% or 30 % that we [indiscernible] [00:05:11] for other means. Maureen Cavanaugh: How long would a vaccine like this lasts, I mean would you get one dose of this vaccine and for the rest of your life if you smoke cigarettes you won’t really feel any effects from nicotine? Jonathan Lockner: Well, Maureen we love to be able to tell people that it’s a one and done type of vaccine but as far as we can see from our own data and from others’ data that it is not the case. In order to maintain sufficient titers, a sufficient number of antibodies against nicotine circulating the bloodstream you need to have booster doses. And so we could envision based on the existing data that an injection schedule of maybe a few injections in the first several months and then boosters thereafter every six months, that might be a practical scheme. Maureen Cavanaugh: Dr. Novotny, smokers who are trying to quit they have a variety of products to help. Let’s go through some of them. There’s a patches, okay. Dr. Thomas Novotny: Well, there’s a nicotine replacement which are patch and then there’s inhalers and– Maureen Cavanaugh: The Chantix, it’s a prescription drugs. Dr. Thomas Novotny: Yeah, that’s another kind of drug, that’s not a nicotine replacement and then there’s also antidepressants like bupropion that are used to help some smokers to get through their addiction. Maureen Cavanaugh: Some people use e-cigarettes. Dr. Thomas Novotny: Well, that’s the advertisement but I am concerned as we’ve been discussing nicotine is a very powerful addictive drug and e-cigarettes I don’t think are going to be a substitute for smoking. Maureen Cavanaugh: Because they still deliver the nicotine? Dr. Thomas Novotny: In ways that we don’t even know, I mean the regulatory structures that have now been put into place on nicotine products like that and I think that they posed a great danger of keeping people addicted rather than getting them off. Maureen Cavanaugh: So, do we know which one of these smoking cessation aids is actually helpful or most helpful? Dr. Thomas Novotny: Well, they all have some benefit and again it ranges from 10, 20 or 30 % in the best cases always accompanied by other kinds of things like counseling which adds to their impact, but also the environment in which a smoker tries to quit. For instance if everybody is smoking around them, their ability to stop smoking is not so great. That’s why we really think that policies also have to be put into place, banning smoking in public places like we have now a ban on smoking on the campus here so that peer pressure or peer sort of acceptability of smoking is not there. Banning advertising, banning the cues to smoke that smokers see every day has been very important in terms of success of quitting. But none of these things function in a vacuum and even the vaccine or any of the therapies at all are all part of a more complex system of multiple efforts to get people not to die from smoking. Maureen Cavanaugh: Some of the prescription drugs out there Chantix, I think there is another one out as well to help people stop smoking have side effects. Some of them are I mean are quite disturbing if indeed you– Dr. Thomas Novotny: Right. Depression etc. even suicide has been linked to it although that’s fallen out of the picture a bit now. Maureen Cavanaugh: Are they effective enough that it is worth that sort of a risk or is the patch just as effective? Dr. Thomas Novotny: You know comparatively I don’t think that there’s been too much done, I mean nicotine replacement again works for some people but I think the biggest thing that works is the decision to quit and that can be assisted by a doctor, if you have to go visit one to get your varenicline or your bupropion that helps a bit. Now with over the counter you can get nicotine replacement but without supporting sort of environment and counseling etc. is not nearly as effective. Maureen Cavanaugh: Jonathan, what about side effects from a potential vaccine, nicotine vaccine. Is it too early to tell at this point? Jonathan Lockner: I think a distinction that needs to be made and emphasized with vaccination compared to bupropion or varenicline and we are just talking about seconds ago about depression as withdrawal symptom and suicidality. You don’t have those types of side effects with a vaccine approach because the vaccine produces antibodies leveraging your own immune system to produce antibodies. And those antibodies are your own and they operate systemically, circulate freely and turn over in the bloodstream. You are not introducing nicotine itself and nicotine replacement therapy or an alternative such as Chantix directly into the brain. And so you’re not introducing side effects in the same way. Perhaps the side effects that are common to other people who are vaccinated, I mean allergic reaction to a vaccine could be anticipated but safety and tolerability has certainly been proven in early stage clinical trials of these vaccines and so I think they are pretty good. Maureen Cavanaugh: I want to follow up on something that you’ve been saying Dr. Novotny because you know there have been great strides made in the US and here in California to decrease the numbers of people who smoke, but worldwide this is still a major health problem. I was reading one billion smokers worldwide. Dr. Thomas Novotny: Right. And you know the same kind of interventions are not possible in many other places in the world although there is now an international treaty Framework Convention on Tobacco Control where 180 countries have signed in on this to cooperate together and that’s important, but you know it’s still the marketing and the indirect sort of marketing effects from movies and television are really powerful drivers of the smoking epidemic. Maureen Cavanaugh: How do you both see? Let me start with you Jonathan. How do you see a successful vaccine against nicotine fitting in the fight against nicotine addiction? Jonathan Lockner: Well I definitely see it happening. I see it happening in the near future. I think that research such as this paper that we are talking about here and further optimization efforts that we hope to make and others, I believe in the field hope to make, will bring a vaccine to the clinic and through the clinic. And I think it’s going to be a powerful compliment to the tools that already exists so the pharmacotherapy’s Chantix and bupropion as well as counseling and I think that when you bring all these to bear you have a much greater likelihood of continuous abstinence in these people who are motivated to quit. Maureen Cavanaugh: Dr. Novotny do you see people getting this before they even start to smoke so that they would never become addicted to nicotine? Dr. Thomas Novotny: That’s a really interesting question because that’s the sort of traditional use of vaccine is to prevent something from happening and I do think of smoking as an infectious disease sort of encouraged among people and certainly there is vector of disease in tobacco industry that likes to spread it. And so if we can think of ways that it could be applied prophylactically I think that would be interesting. I think theoretically it’s possible but as you point out you know the booster effect is not something probably that would be practical in terms of primary prevention. Jonathan Lockner: Yeah the booster idea that we talked about before and now we are talking about prophylaxis. If another one of the parameters that remains to be optimized that being the ability of the vaccine, one shot of the vaccine to potentiate a response and that response to last for a long time. If we can optimize that parameter and have ideally the optimum goal would be one and done. If we can achieve that then the idea of prophylaxis could be something for further discussion. Dr. Thomas Novotny: That would be really exciting. I’d like to bring in one other piece here that there’s another approach that has been proposed. It’s kind of some of the same sort of objective and that is to remove nicotine from the equation and that’s fading of nicotine in cigarettes and [indiscernible] [00:13:38] and other colleagues have proposed this back as far as 1994 to gradually in the commercial product reduce the amount of nicotine overtime so that people basically are being withdrawn without them knowing it. Maureen Cavanaugh: And that would be through legislation? Dr. Thomas Novotny: Well that will be through product regulation and now we have that with the FDA. They could do it. They can’t get it down to zero but they can get it close to zero which would probably not be then an additive product. Maureen Cavanaugh: I’ve got to end it there. I have been speaking with Jonathan Lockner, Research Associate at Scripps Research Institute and Dr. Thomas Novotny, Professor, Co-Director of the Joint Degree Program in Global Health here at San Diego State. Thank you both. Dr. Thomas Novotny: Thank you. Jonathan Lockner: Thanks Maureen.

Scientists at The Scripps Research Institute announced Monday that they've come up with a way to create a more effective nicotine vaccine, which could eventually help people trying to quit smoking from relapsing.

In a study published in the Journal of Medicinal Chemistry, the researchers said they discovered which is the best target of two types of nicotine, which are referred to as left-handed and right-handed.

According to the institute, 99 percent of the nicotine molecules in tobacco are of the left-handed variety. A once-promising nicotine vaccine that went through clinical trials a few years ago didn't distinguish between the two sides and ended up working in only 30 percent of test subjects.

Smoking is the leading cause of eight forms of cancer, including lung and fast-moving pancreatic types of the disease, according to the National Cancer Institute.

Researchers are hoping that a vaccine will create antibodies that will shut off the brain's reward system for nicotine.

"This is just one area where we are looking outside the box to try to treat addiction," said Kim Janda, the Ely R. Callaway Jr. professor of chemistry and member of the Skaggs Institute for Chemical Biology at the institute.

He said vaccines that target left- or right-handedness of molecules could help treat cocaine and heroin addiction.

Jonathan Lockner, a research associate for The Scripps Research Institute, told KPBS Midday Edition on Tuesday that researchers predict smokers will need several injections for the first few months then booster injections every six months.

But former Assistant Surgeon General Thomas Novotny told KPBS that motivation is a factor to quitting the habit.

"If a smoker is motivated to quit, most of the time the smokers can quit on their own," Novotny said. "But for some smokers, they need a little boost."

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