The Experts below are selected from a list of 444 Experts worldwide ranked by ideXlab platform
Paul R. Pentel - One of the best experts on this subject based on the ideXlab platform.
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Alum as an adjuvant for nanoparticle based Vaccines: A case study with a hybrid nanoparticle-based Nicotine Vaccine.
Nanomedicine : nanotechnology biology and medicine, 2019Co-Authors: Daniel G. A. Smith, Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Abstract The treatment efficacy of a Nicotine Vaccine largely relies on its ability to induce high titers of Nicotine-specific antibodies. Due to its strong immune-potentiating effects, aluminum salt (Alum) has been commonly used as an adjuvant in various Nicotine Vaccine formulations. In this study, we attempted to improve the immunological performance of a hybrid nanoparticle-based Nicotine Vaccine (NanoNicVac) by co-administering it with Alum. It was found that Alum severely restricted the release of NanoNicVac at the site of injection. Moreover, Alum damaged the hybrid structure of the Vaccine. In the animal trial, mice immunized with NanoNicVac alone achieved an anti-Nicotine IgG titer of 3.5 ± 0.2 × 104 after three injections. Unexpectedly, Alum with quantities of 125, 250, 500, and 1000 μg did not enhance the immunogenicity of NanoNicVac. In addition, Alum did not improve the ability of the Vaccine to reduce the entry of Nicotine into the brain.
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Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine.
Molecular pharmaceutics, 2019Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Adjuvants are a critical component for Vaccines, especially for a poorly immunogenic antigen, such as Nicotine. However, the impact of adjuvant release rate from a Vaccine formulation on its immunogenicity has not been well illustrated. In this study, we fabricated a series of hybrid-nanoparticle-based Nicotine Vaccines to study the impact of adjuvant release rate on their immunological efficacy. It was found that the nanoVaccine with a medium or slow adjuvant release rate induced a significantly higher anti-Nicotine antibody titer than that with a fast release rate. Furthermore, the medium and slow adjuvant release rates resulted in a significantly lower brain Nicotine concentration than the fast release rate after Nicotine challenge. All findings suggest that adjuvant release rate affects the immunological efficacy of nanoparticle-based Nicotine Vaccines, providing a potential strategy to rationally designing Vaccine formulations against psychoactive drugs or even other antigens. The hybrid-nanoparticle...
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Paradox of PEGylation in fabricating hybrid nanoparticle-based Nicotine Vaccines.
Biomaterials, 2018Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Abstract Polyethylene glycol (PEG) has long been used in nanoparticle-based drug or Vaccine delivery platforms. In this study, nano-Nicotine Vaccines (NanoNicVac) were PEGylated to different degrees to investigate the impact of PEG on the immunological efficacy of the Vaccine. Hybrid nanoparticles with various degrees of PEGylation (2.5%–30%) were assembled. It was found that 30% PEGylation resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles by dendritic cells. However, increasing the quantity of the PEG could effectively reduce nanoparticle aggregation during storage and improve the stability of the hybrid nanoparticles. Subsequently, Nicotine Vaccines were synthesized by conjugating Nicotine haptens to the differently PEGylated hybrid nanoparticles. In both in vitro and in vivo studies, it was found that a Nicotine Vaccine with 20% PEGylation (NanoNicVac 20.0) was significantly more stable than the Vaccines with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly higher anti-Nicotine antibody titer of 3.7 ± 0.6 × 104 in mice than the other NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic study, the lowest brain Nicotine concentration of 34 ± 11 ng/g was detected in mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse events were observed in mice immunized with NanoNicVac. In summary, 20% PEGylation confers NanoNicVac with desirable safety, the highest stability, and the best immunological efficacy in mice.
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Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based Nicotine Vaccine for immunotherapy against Nicotine addiction.
Biomaterials, 2017Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Brian Harris, Chenming ZhangAbstract:Current clinically-tested Nicotine Vaccines have yet shown enhanced smoking cessation efficacy due to their low immunogenicity. Achieving a sufficiently high immunogenicity is a necessity for establishing a clinically-viable Nicotine Vaccine. This study aims to facilitate the immunogenicity of a hybrid nanoparticle-based Nicotine Vaccine by rationally incorporating toll-like receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA), Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their combinations. The nanoparticle-delivered model adjuvant was found to be taken up more efficiently by dendritic cells than the free counterpart. NanoVaccine particles were transported to endosomal compartments upon cellular internalization. The incorporation of single or dual TLR adjuvants not only considerably increased total anti-Nicotine IgG titers but also significantly affected IgG subtype distribution in mice. Particularly, the nanoVaccines carrying MPLA+R848 or MPLA+ODN 1826 generated a much higher anti-Nicotine antibody titer than those carrying none or one adjuvant. Meanwhile, the anti-Nicotine antibody elicited by the nanoVaccine adjuvanted with MPLA+R848 had a significantly higher affinity than that elicited by the nanoVaccine carrying MPLA+ODN 1826. Moreover, the incorporation of all the selected TLR adjuvants (except MPLA) reduced the brain Nicotine levels in mice after Nicotine challenge. Particularly, the nanoVaccine with MPLA+R848 exhibited the best ability to reduce the level of Nicotine entering the brain. Collectively, rational incorporation of TLR adjuvants could enhance the immunological efficacy of the hybrid nanoparticle-based Nicotine Vaccine, making it a promising next-generation immunotherapeutic candidate for treating Nicotine addiction.
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Rationalization of a nanoparticle-based Nicotine nanoVaccine as an effective next-generation Nicotine Vaccine: A focus on hapten localization.
Biomaterials, 2017Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:A lipid-polymeric hybrid nanoparticle-based next-generation Nicotine nanoVaccine was rationalized in this study to combat Nicotine addiction. A series of nanoVaccines, which had Nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanoVaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against Nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-Nicotine antibodies elicited by LPKN and LPNKN bind Nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block Nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based Nicotine Vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting Nicotine addiction.
Onno C. P. Van Schayck - One of the best experts on this subject based on the ideXlab platform.
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Lifestyle Vaccines and Public Health: Exploring Policy Options for a Vaccine to Stop Smoking
Public health ethics, 2016Co-Authors: Anna Wolters, Onno C. P. Van Schayck, Guido De Wert, Klasien HorstmanAbstract:Experimental Vaccines are being developed for the treatment of 'unhealthy lifestyles' and associated chronic illnesses. Policymakers and other stakeholders will have to deal with the ethical issues that this innovation path raises: are there morally justified reasons to integrate these innovative biotechnologies in future health policies? Should public money be invested in further research? Focusing on the case of an experimental Nicotine Vaccine, this article explores the ethical aspects of 'lifestyle Vaccines' for public health. Based on findings from a qualitative study into a Vaccine for smoking cessation, the article articulates possible value conflicts related to Nicotine vaccination as an intervention in tobacco control. The 'vaccinization' of lifestyle disease piggybacks on the achievements of classic Vaccines. Contrary to expectations of simplicity and success, quitting smoking with a Vaccine requires a complex supportive network. Social justice and public trust may become important ethical challenges when deciding whether to use further public funds for research or whether to implement these innovative Vaccines in the future.
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treatment with a Nicotine Vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task
Addiction, 2014Co-Authors: Eric F. P. M. Vuurman, Anne Havermans, Job Van Den Hurk, Philippe Hoogsteder, Onno C. P. Van SchayckAbstract:Aims To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. Design Randomized, placebo-controlled parallel-group, repeated-measures design. Setting Maastricht University, the Netherlands. Participants Forty-eight male smokers were randomized to receive five injections with either 400 μg/ml of the 3′-aminomethylNicotine Pseudomonas aeruginosa r-Exoprotein-conjugated Vaccine or placebo. Subjects were tested on two occasions, once after a Nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. Measurements Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent (BOLD) response was measured during this task and during smoking cue exposure. Findings Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus (P < 0.005); however, this effect did not survive correction for multiple comparisons. There was no difference in brain activity to smoking cues between the treatment groups and no effects of acute Nicotine challenge were established. For the n-back task we found working memory load-sensitive increases in brain activity in several frontal and parietal areas (P < 0.0025). However, no effects of immunization or Nicotine challenge were observed. Conclusion No significant effects of immunization on brain activity in response to a Nicotine challenge were established. Therefore this Vaccine is not likely to be an effective aid in smoking cessation.
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Efficacy of the Nicotine Vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial
Addiction (Abingdon England), 2014Co-Authors: Philippe Hj Hoogsteder, Daniel Kotz, Paul I. Van Spiegel, Wolfgang Viechtbauer, Onno C. P. Van SchayckAbstract:Background and Aims Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the Nicotine Vaccine 3′-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention. Design Randomized placebo-controlled trial. Setting Two research centres (Maastricht University Medical Centre and Slotervaart Hospital) in the Netherlands. Participants A total of 558 smokers were assigned randomly to six injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with open label varenicline and behavioural support. Measures Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to 52 (secondary). We also performed a pre-planned subgroup analysis in the top 30% antibody responders. Findings There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62–1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73–1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89–2.42). Conclusion The Nicotine Vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.
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Treatment with a Nicotine Vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task
Addiction (Abingdon England), 2014Co-Authors: Anne Havermans, Eric F. P. M. Vuurman, Job Van Den Hurk, Philippe Hoogsteder, Onno C. P. Van SchayckAbstract:Aims To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. Design Randomized, placebo-controlled parallel-group, repeated-measures design. Setting Maastricht University, the Netherlands. Participants Forty-eight male smokers were randomized to receive five injections with either 400 μg/ml of the 3′-aminomethylNicotine Pseudomonas aeruginosa r-Exoprotein-conjugated Vaccine or placebo. Subjects were tested on two occasions, once after a Nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. Measurements Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent (BOLD) response was measured during this task and during smoking cue exposure. Findings Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus (P
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Constructing a trial as a personal lifestyle change project: Participants' experiences in a clinical study for Nicotine vaccination
Social science & medicine (1982), 2013Co-Authors: Anna Wolters, Onno C. P. Van Schayck, Guido De Wert, Klasien HorstmanAbstract:Abstract The purpose of this study was to gain insight into the experiences and dynamics of the involvement of research participants in a randomized clinical trial for Nicotine vaccination. Participants received an experimental Nicotine Vaccine or a placebo, in addition to quit smoking medication and counseling. The longitudinal design of this qualitative study allowed us to follow people from their first visit to the trial location until the unblinding of their treatment with either verum or placebo Vaccine. The empirical data consisted of 49 semi-structured, in-depth interviews, field notes and memos, and trial documents collected in the Netherlands between 2010 and 2012. Participants' expectations and experiences of the innovative Nicotine Vaccine were characterized by ambivalence: Although they complied with the research design, throughout the study they tinkered with discourses, objects, and activities to make them serve their individual goals. They made the concepts of Nicotine vaccination and placebo treatment meaningful for quitting, reshaped the meaning of research tests and obligatory visits to serve their own personal goals, and introduced a new element into the trial by creating space to discuss problems that might endanger the quit attempt. In short, the participants constructed the clinical study for Nicotine vaccination as their own personal lifestyle change project.
Chenming Zhang - One of the best experts on this subject based on the ideXlab platform.
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Toll-like Receptor 9 Agonists as Adjuvants for Nanoparticle-Based Nicotine Vaccine
Molecular pharmaceutics, 2021Co-Authors: Daniel G. A. Smith, Zongmin Zhao, Evan Frazier, Chenming ZhangAbstract:Nicotine Vaccine was considered a promising therapy against smoking addiction. The level of immune response that a Nicotine Vaccine can induce is pivotal to its efficacy. In this study, Toll-like receptor 9 agonists, namely, CpG ODN 1555 and CpG ODN 1826, were incorporated into a nanoparticle-based Nicotine Vaccine (NanoNicVac) to enhance its immunogenicity. The results showed that NanoNicVac containing either CpG ODN 1555 or CpG ODN 1826 could be rapidly internalized by dendritic cells. In mice trials, it was found that NanoNicVac with CpG ODN 1555 and CpG ODN 1826 induced 3.3- and 3.2-fold higher anti-Nicotine antibody titer than that by the native NanoNicVac after two injections, respectively. Instead of enhancing the immunogenicity of the Vaccine, however, mixtures of the two CpG ODNs were observed to exert an immune-suppressing effect on NanoNicVac. Finally, the histopathological examination on major organs of the mice immunized with the NanoNicVacs proved that NanoNicVac with either CpG ODN 1555 or CpG ODN 1826 as adjuvants did not cause detectable toxicity to the mice.
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Alum as an adjuvant for nanoparticle based Vaccines: A case study with a hybrid nanoparticle-based Nicotine Vaccine.
Nanomedicine : nanotechnology biology and medicine, 2019Co-Authors: Daniel G. A. Smith, Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Abstract The treatment efficacy of a Nicotine Vaccine largely relies on its ability to induce high titers of Nicotine-specific antibodies. Due to its strong immune-potentiating effects, aluminum salt (Alum) has been commonly used as an adjuvant in various Nicotine Vaccine formulations. In this study, we attempted to improve the immunological performance of a hybrid nanoparticle-based Nicotine Vaccine (NanoNicVac) by co-administering it with Alum. It was found that Alum severely restricted the release of NanoNicVac at the site of injection. Moreover, Alum damaged the hybrid structure of the Vaccine. In the animal trial, mice immunized with NanoNicVac alone achieved an anti-Nicotine IgG titer of 3.5 ± 0.2 × 104 after three injections. Unexpectedly, Alum with quantities of 125, 250, 500, and 1000 μg did not enhance the immunogenicity of NanoNicVac. In addition, Alum did not improve the ability of the Vaccine to reduce the entry of Nicotine into the brain.
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Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine.
Molecular pharmaceutics, 2019Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Adjuvants are a critical component for Vaccines, especially for a poorly immunogenic antigen, such as Nicotine. However, the impact of adjuvant release rate from a Vaccine formulation on its immunogenicity has not been well illustrated. In this study, we fabricated a series of hybrid-nanoparticle-based Nicotine Vaccines to study the impact of adjuvant release rate on their immunological efficacy. It was found that the nanoVaccine with a medium or slow adjuvant release rate induced a significantly higher anti-Nicotine antibody titer than that with a fast release rate. Furthermore, the medium and slow adjuvant release rates resulted in a significantly lower brain Nicotine concentration than the fast release rate after Nicotine challenge. All findings suggest that adjuvant release rate affects the immunological efficacy of nanoparticle-based Nicotine Vaccines, providing a potential strategy to rationally designing Vaccine formulations against psychoactive drugs or even other antigens. The hybrid-nanoparticle...
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Nicotine Vaccines: The Past, the Present, and the Future
Neuroscience of Nicotine, 2019Co-Authors: Zongmin Zhao, Kyle Saylor, Chenming ZhangAbstract:Abstract Smoking has become one of the most destructive habits that humans have ever participated in. To address the issue, various therapies have been developed over the years that have targeted the major addictive component of smoking, Nicotine. These therapies have struggled to address the growing epidemic due to their numerous and well-known limitations; however, currently, there is no go-to treatment plan for Nicotine addiction. An alternative, less known form of therapy for Nicotine addiction, immunopharmacotherapy, is currently in development and has shown exceptional promise in past animal studies. Vaccine candidates that have arisen from these studies have ultimately met failure in clinical trials, however, due to the lack of observed efficacy in the majority of study participants. Undeterred, current Nicotine Vaccine research continues and focuses on overcoming the limitations observed in previous Vaccines through the optimization of existing technologies and the implementation of novel ideas. It seems likely that with enough time, support, and collaboration, an effective Nicotine Vaccine will someday make it to the market.
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Paradox of PEGylation in fabricating hybrid nanoparticle-based Nicotine Vaccines.
Biomaterials, 2018Co-Authors: Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, Chenming ZhangAbstract:Abstract Polyethylene glycol (PEG) has long been used in nanoparticle-based drug or Vaccine delivery platforms. In this study, nano-Nicotine Vaccines (NanoNicVac) were PEGylated to different degrees to investigate the impact of PEG on the immunological efficacy of the Vaccine. Hybrid nanoparticles with various degrees of PEGylation (2.5%–30%) were assembled. It was found that 30% PEGylation resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles by dendritic cells. However, increasing the quantity of the PEG could effectively reduce nanoparticle aggregation during storage and improve the stability of the hybrid nanoparticles. Subsequently, Nicotine Vaccines were synthesized by conjugating Nicotine haptens to the differently PEGylated hybrid nanoparticles. In both in vitro and in vivo studies, it was found that a Nicotine Vaccine with 20% PEGylation (NanoNicVac 20.0) was significantly more stable than the Vaccines with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly higher anti-Nicotine antibody titer of 3.7 ± 0.6 × 104 in mice than the other NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic study, the lowest brain Nicotine concentration of 34 ± 11 ng/g was detected in mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse events were observed in mice immunized with NanoNicVac. In summary, 20% PEGylation confers NanoNicVac with desirable safety, the highest stability, and the best immunological efficacy in mice.
Dorothy K Hatsukami - One of the best experts on this subject based on the ideXlab platform.
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Immunogenicity and Smoking Cessation Outcomes for a Novel Nicotine Immunotherapeutic
2016Co-Authors: Dorothy K Hatsukami, Douglas E Jorenby, David Gonzales, Nancy A. Rigotti, Roxanne C. Akhavain, Elbert D, Cheryl A. Oncken, Donald P. Tashkin, Victor I. Reus, Raafat E. F. FahimAbstract:NicVAX®, a Nicotine Vaccine (3’AmNic-rEPA), has been clinically evaluated to determine if higher antibody concentrations are associated with higher smoking abstinence rates and if doses and frequency of administration are associated with increased antibody response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N=301 smokers) tested 200 and 400 µg doses administered 4 or 5 times over 6 months compared to placebo. 3’AmNic-rEPA recipients with the highest serum anti-Nicotine antibody response (top 30 % by AUC) were Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research
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The Cochrane Library - Nicotine Vaccines for smoking cessation.
The Cochrane database of systematic reviews, 2012Co-Authors: Jamie Hartmann-boyce, Dorothy K Hatsukami, Kate Cahill, Jacques CornuzAbstract:Background By reducing the amount of Nicotine that reaches the brain when a person smokes a cigarette, Nicotine Vaccines may help people to stop smoking or to prevent recent quitters from relapsing. Objectives The aims of this review are to assess the efficacy of Nicotine Vaccines for smoking cessation and for relapse prevention, and to assess the frequency and type of adverse events associated with the use of Nicotine Vaccines. Search methods We searched the Cochrane Tobacco Addiction Review Group specialised register for trials, using the term 'Vaccine' in the title or abstract, or in a keyword (date of most recent search April 2012). To identify any other material including reviews and papers potentially relevant to the background or discussion sections, we also searched MEDLINE, EMBASE, and PsycINFO, combining terms for Nicotine Vaccines with terms for smoking and tobacco use, without design limits or limits for human subjects. We searched the Annual Meeting abstracts of the Society for Research on Nicotine and Tobacco up to 2012, using the search string 'vaccin'. We searched Google Scholar for 'Nicotine Vaccine'. We also searched company websites and Google for information related to specific Vaccines. We searched clinicaltrials.gov in March 2012 for 'Nicotine Vaccine' and for the trade names of known Vaccine candidates. Selection criteria We included randomized controlled trials of Nicotine Vaccines, at Phase II and Phase III trial stage and beyond, in adult smokers or recent ex-smokers. We included studies of Nicotine Vaccines used as part of smoking cessation or relapse prevention interventions. Data collection and analysis We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, blinding of participants and personnel, reporting of outcomes, and completeness of follow-up. Our primary outcome measure was a minimum of six months abstinence from smoking. We used the most rigorous definition of abstinence, and preferred cessation rates at 12 months and biochemically validated rates where available. We have used the risk ratio (RR) to summarize individual trial outcomes. We have not pooled the current group of included studies as they cover different Vaccines and variable regimens. Main results There are no Nicotine Vaccines currently licensed for public use, but there are a number in development. We found four trials which met our inclusion criteria, three comparing NicVAX to placebo and one comparing NIC002 (formerly NicQbeta) to placebo. All were smoking cessation trials conducted by pharmaceutical companies as part of the drug development process, and all trials were judged to be at high or unclear risk of bias in at least one domain. Overall, 2642 smokers participated in the included studies in this review. None of the four included studies detected a statistically significant difference in long-term cessation between participants receiving Vaccine and those receiving placebo. The RR for 12 month cessation in active and placebo groups was 1.35 (95% Confidence Interval (CI) 0.82 to 2.22) in the trial of NIC002 and 1.74 (95% CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which full results were not available, reported similar quit rates of approximately 11% in both groups. In the two studies with full results available, post hoc analyses detected higher cessation rates in participants with higher levels of Nicotine antibodies, but these findings are not readily generalisable. The two studies with full results showed Nicotine Vaccines to be well tolerated, with the majority of adverse events classified as mild or moderate. In the study of NIC002, participants receiving the Vaccine were more likely to report mild to moderate adverse events, most commonly flu-like symptoms, whereas in the study of NicVAX there was no significant difference between the two arms. Information on adverse events was not available for the large Phase III trials of NicVAX. Vaccine candidates are likely to undergo significant changes before becoming available to the general public, and those included in this review may not be the first to reach market; this limits the external validity of the results reported in this review in terms of both effectiveness and tolerability. Authors' conclusions There is currently no evidence that Nicotine Vaccines enhance long-term smoking cessation. Rates of serious adverse events recorded in the two trials with full data available were low, and the majority of adverse events reported were at mild to moderate levels. The evidence available suggests Nicotine Vaccines do not induce compensatory smoking or affect withdrawal symptoms. No Nicotine Vaccines are currently licensed for use in any country but a number are under development. Further trials of Nicotine Vaccines are needed, comparing Vaccines with placebo for smoking cessation. Further trials are also needed to explore the potential of Nicotine Vaccines to prevent relapse. Results from past, current and future research should be reported in full. Adverse events and serious adverse events should continue to be carefully monitored and thoroughly reported.
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immunogenicity and smoking cessation outcomes for a novel Nicotine immunotherapeutic
Clinical Pharmacology & Therapeutics, 2011Co-Authors: Dorothy K Hatsukami, Douglas E Jorenby, David Gonzales, Nancy A. Rigotti, Roxanne C. Akhavain, Cheryl A. Oncken, Donald P. Tashkin, Victor I. Reus, Elbert D Glover, Raafat FahimAbstract:NicVAX, a Nicotine Vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antiNicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to Nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for Nicotine dependence is therefore justified.
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Abstract 3712: A Randomized Placebo-Controlled Trial of a Conjugate Nicotine Vaccine (NicVAX(R)) in Smokers Who Want to Quit: 12 Month Results
Circulation, 2007Co-Authors: Stephen I Rennard, Arjen De Vos, Douglas E Jorenby, David Gonzales, Nancy A. Rigotti, Enoch B Bortey, Roxanne C. Akhavain, Dorothy K HatsukamiAbstract:Background: Cigarette smoking triples the risk of dying from heart disease among middle-aged men and women. A Nicotine Vaccine (NicVAX®) has been developed to produce Nicotine-specific antibodies as a means of reducing entry of Nicotine into the brain as an aid to smoking cessation. Objective: To assess 12-month safety, efficacy and immunogenicity of NicVAX in smokers who want to quit. Method: Randomized, double-blinded, placebo-controlled multicenter clinical trial with 2 dose levels of NicVAX (200μg & 400μg) and 2 schedules. Generally healthy adults who smoked ≥ 15 cigarettes/day were recruited. Subjects were randomized 2:1, active:placebo, at 9 sites in the US. The primary endpoint was self reported continuous abstinence for weeks 19 – 26 confirmed by expired CO levels of ≤ 8 ppm. Secondary endpoints include point prevalence abstinence at 12 months. Results: 301 subjects (52% female) with a mean age of 48, smoking on average 24 cigarettes/day were enrolled. A pre-defined analysis of antibody levels for subjects receiving NicVAX were reviewed and divided into low and high responder groups, with the top 30 th percentile representing the high responder group. Analysis for the primary endpoint demonstrated that 15/61 (24.6%) of subjects having the highest antibody titers achieved an 8 week period of continuous abstinence between weeks 19 –26, compared to 13/100 (13.0%) for the subjects who received placebo (p=0.04). In contrast, the quit rate for those subjects that did not achieve a high antibody titer was not significantly different from placebo (14/140, 10%). There was a significant relationship between anti-Nicotine antibody levels and continuous abstinence from smoking (p=0.0001). NicVAX was well-tolerated and showed no differences in adverse events or in local/systemic reactions between placebo and each active Vaccine group. Conclusion: Proof-of-concept has been established by the strong correlation of high antibody titers with smoking abstinence. Interim data (6 months post vaccination) demonstrate that generating antibodies to Nicotine may be a useful approach for aiding smoking cessation. This study will be completed in Sept 2007. Immunogenicity, sustained smoking cessation and relapse rates at 12 months after vaccination will be presented.
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safety and immunogenicity of a Nicotine conjugate Vaccine in current smokers
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Dorothy K Hatsukami, Arjen De Vos, Gary Horwith, Stephen I Rennard, Douglas E Jorenby, Mph Michael Fiore, Joseph S Koopmeiners, Paul R. PentelAbstract:Immunotherapy is a novel potential treatment for Nicotine addiction. The aim of this study was to assess the safety and immunogenicity of a Nicotine conjugate Vaccine, NicVAX, and its effects on smoking behavior. Smokers (N = 68) were recruited for a noncessation treatment study and assigned to 1 of 3 doses of the Nicotine Vaccine (50, 100, or 200 μg) or placebo. They were injected on days 0, 28, 56, and 182 and monitored for a period of 38 weeks. Results showed that the Nicotine Vaccine was safe and well tolerated. Vaccine immunogenicity was dose-related (P<.001), with the highest dose eliciting antibody concentrations within the anticipated range of efficacy. There was no evidence of compensatory smoking or precipitation of Nicotine withdrawal with the Nicotine Vaccine. The 30-day abstinence rate was significantly different across the 4 doses (P = .02), with the highest rate of abstinence occurring with 200 μg. The Nicotine Vaccine appears to be a promising medication for tobacco dependence. Clinical Pharmacology & Therapeutics (2005) 78, 456–467; doi: 10.1016/j.clpt.2005.08.007
Philippe Hj Hoogsteder - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of the Nicotine Vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial
Addiction (Abingdon England), 2014Co-Authors: Philippe Hj Hoogsteder, Daniel Kotz, Paul I. Van Spiegel, Wolfgang Viechtbauer, Onno C. P. Van SchayckAbstract:Background and Aims Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the Nicotine Vaccine 3′-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention. Design Randomized placebo-controlled trial. Setting Two research centres (Maastricht University Medical Centre and Slotervaart Hospital) in the Netherlands. Participants A total of 558 smokers were assigned randomly to six injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with open label varenicline and behavioural support. Measures Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to 52 (secondary). We also performed a pre-planned subgroup analysis in the top 30% antibody responders. Findings There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62–1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73–1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89–2.42). Conclusion The Nicotine Vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.
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Efficacy of the Nicotine Vaccine 3'-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial
'Wiley', 2014Co-Authors: Philippe Hj Hoogsteder, Kotz Daniel, Van Spiegel Paul, Viechtbauer Wolfgang, Onno Cp ,van SchayckAbstract:Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the Nicotine Vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention.status: publishe
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The efficacy and safety of a Nicotine conjugate Vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial
BMC public health, 2012Co-Authors: Philippe Hj Hoogsteder, Daniel Kotz, Paul I. Van Spiegel, Wolfgang Viechtbauer, Raafat E. F. Fahim, Ruth Brauer, Paul D. Kessler, Matthew W Kalnik, Onno C. P. Van SchayckAbstract:A potential new treatment in smoking cessation and relapse prevention is Nicotine vaccination which is based on active immunization against the Nicotine molecule. This immunization will elicit the immune system to produce Nicotine-specific antibodies that sequester Nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of Nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the Nicotine Vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention.
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The efficacy and safety of a Nicotine conjugate Vaccine (NicVAX^®) or placebo co-administered with varenicline (Champix^®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial
BMC Public Health, 2012Co-Authors: Philippe Hj Hoogsteder, Daniel Kotz, Paul I. Van Spiegel, Wolfgang Viechtbauer, Raafat E. F. Fahim, Ruth Brauer, Paul D. Kessler, Matthew W Kalnik, Onno C. P. Van SchayckAbstract:Background A potential new treatment in smoking cessation and relapse prevention is Nicotine vaccination which is based on active immunization against the Nicotine molecule. This immunization will elicit the immune system to produce Nicotine-specific antibodies that sequester Nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of Nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the Nicotine Vaccine NicVAX^® co-administered with varenicline (Champix^®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week −2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX^® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a Nicotine conjugate Vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX^® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of Nicotine vaccination for relapse prevention. Trial registration ClinicalTrials.gov: (NCT00995033)