Nanoparticle-Based Nicotine Vaccine

Ilyinskii, Petr O.; Johnston, Lloyd

doi:10.1007/978-3-319-23150-1_14

Cited by 4 publications

(8 citation statements)

References 87 publications

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“…As a result, adjuvants cannot be targeted to APCs specifically and thus are poorly available to APCs. [13] The design of NanoNicVac particles can overcome the abovementioned drawbacks of CNVs. On one hand, NanoNicVac particles provide a host for the loading of protein antigens and molecular adjuvants.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, even with the help of alum to form particulate particles, CNVs cannot be easily tuned to have optimal physicochemical properties (such as size, shape, and charge) for cellular uptake. [13, 14] Moreover, molecular adjuvants cannot be easily incorporated into CNVs, and they are typically co-administered with CNVs via physical mixing. In this way, molecular adjuvants are not specifically available to immune cells and their release cannot be controlled in immune cells, thus leading to low adjuvant efficacy and systemic toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…In this way, molecular adjuvants are not specifically available to immune cells and their release cannot be controlled in immune cells, thus leading to low adjuvant efficacy and systemic toxicity. [13, 15, 16]…”

Section: Introductionmentioning

confidence: 99%

“…The lipid-shell and PLGA-core served as hosts for cell-surface-TLR and endosomal-TLR agonists, respectively. Monophosphoryl lipid A (MPLA),[31, 32] Resiquimod (R848),[13, 33] and CpG oligodeoxynucleotide 1826 (CpG ODN 1826),[34, 35] all of which have been reported to significantly enhance immune responses, were selected as adjuvant candidates. In this study, NanoNicVac particles carrying different TLR adjuvants or combinations were fabricated, and their physicochemical properties were characterized.…”

Section: Introductionmentioning

confidence: 99%

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Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction

Zhao

Harris

et al. 2018

Biomaterials

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction

Zhao

Harris

et al. 2018

Biomaterials

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“…8,9 Unfortunately, none of these CNVs, except NIC7, which is still ongoing in a phase I clinical trial, achieved an enhanced overall smoking cessation rate. 9 Despite this failure, these clinical trials offered two valuable pieces of information to researchers. First, the basic concept of using immunotherapy for treating nicotine addiction is fundamentally sound, as subjects with the highest anti-nicotine antibody titers showed an enhanced smoking cessation rate.…”

Section: ■ Introductionmentioning

confidence: 99%

Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine

Zhao¹,

Hu²,

Harmon

et al. 2019

Mol. Pharmaceutics

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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 hybridnanoparticle-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-based nicotine vaccine with an optimized adjuvant release rate can be a promising next-generation immunotherapeutic candidate against nicotine.

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Current status and future prospects for the development of substance abuse vaccines

Heekin

Shorter

Kosten

2017

Expert Review of Vaccines

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Substance use disorders (SUD) are a significant threat to both individual and public health. To date, SUD pharmacotherapy has focused primarily on agonist medications (i.e. nicotine replacement therapy for tobacco use disorder; methadone and buprenorphine for opioid use disorder), antagonist medications (i.e. naltrexone for opioid use disorder), and aversive therapy (i.e. disulfiram for alcohol use disorder). Pharmacotherapeutic approaches utilizing an immunological framework for medication development represent an important focus of study for treatment of these illnesses. Areas covered: This review discusses vaccines for treatment of substance use disorders. Using PubMed ( https://www.ncbi.nlm.nih.gov/pubmed/ ), we searched both preclinical and human clinical trials of vaccines for treatment of nicotine, cocaine, methamphetamine, and opioid use disorders. In addition, we searched for recently developed strategies for enhancement of the immunologic response through alteration of conjugate molecules and adjuvants. Expert commentary: Despite challenges in human clinical trials of SUD vaccines, a number of strategies have been introduced which may ultimately improve efficacy. These challenges, as well as their implications for vaccine development, are discussed. Additionally, the optimal conditions for research study and treatment are considered.

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Nanoparticle-Based Nicotine Vaccine

Cited by 4 publications

References 87 publications

Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction

Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction

Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine

Current status and future prospects for the development of substance abuse vaccines

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