The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

Hu, Yun; Smith, Daniel A.; Frazier, Evan; Hoerle, Reece; Ehrich, Marion; Zhang, Chenming

doi:10.1016/j.biomaterials.2016.08.028

Cited by 36 publications

(113 citation statements)

References 66 publications

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“…In both IL-4 depleted mice and IL-4 −/− mice, greater vaccine efficacy against oxycodone was associated with increased IgG 2a and IgG 3 antibody titers. This finding is consistent with other reports that active immunization against drugs of abuse benefits from a mixed Th 1 /Th 2 response 50 – 54 , but its biological relevance remains unknown. We hypothesized that IgG-dependent effector functions may be involved at least in part in vaccine efficacy against drugs of abuse.…”

Section: Resultssupporting

confidence: 92%

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Laudenbach

Baruffaldi

Robinson

et al. 2018

Sci Rep

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Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.

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Section: Resultssupporting

confidence: 92%

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Laudenbach

Baruffaldi

Robinson

et al. 2018

Sci Rep

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“…Nicotine vaccines hold a great promise for anti-nicotine immunotherapy [35]. Despite the unsatisfied clinical outcomes of several nicotine vaccines (NicVAX, NicQb, Niccine) [35][36][37], different strategies are under exploration to improve anti-nicotine immunotherapy that include improved vaccine carriers [25,[38][39][40][41][42][43][44][45]. KLH was found to be a more immunogenic carrier than recombinant Pseudomonas Exoprotein A (rEPA) used in NicVAX for nicotine vaccine development [46].…”

Section: More Immunogenic Fh Vlps Than Fljb Hbc Vlps or Klh For Nicomentioning

confidence: 99%

Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on virus-like particle surface

Zhao

Zhu

et al. 2020

Biomaterials

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Flagellin is a protein-based adjuvant that activates toll-like receptor (TLR) 5. Flagellin has been actively explored as vaccine adjuvants and carriers. Preclinical and clinical studies find flagellinbased vaccines have a risk to induce systemic adverse reactions potentially due to its overt activation of TLR5. To improve safety and immunogenicity of flagellin as vaccine carriers, FljB was displayed at high densities on hepatitis b core (HBc) virus-like particle (VLP) surface upon c/e1 loop insertion. FljB-HBc (FH) VLPs showed significantly reduced ability to activate TLR5 or induce systemic interleukin-6 release as compared to FljB. FH VLPs also failed to significantly increase rectal temperature of mice, while FljB could significantly increase rectal temperature of mice. These data indicated systemic safety of FljB could be significantly improved by high-density display on HBc VLP surface. Besides improved safety, FH VLPs and FljB similarly boosted co-administered ovalbumin immunization and FH VLPs were found to induce twofold higher anti-FljB antibody titer than FljB. These data indicated preserved adjuvant potency and improved immunogenicity after high-density display of FljB on HBc VLP surface. Consistent with the high immunogenicity, FH VLPs were found to be more efficiently taken up by bone marrow-derived dendritic cells (BMDCs) and stimulate more potent DC maturation than FljB. Lastly, FH VLPs were found to be a more immunogenic carrier than FljB, HBc VLPs, or the widely used keyhole limpet hemocyanin for nicotine vaccine development with good local and systemic safety. Our data support FH VLPs to be a potentially safer and more immunogenic carrier than FljB for vaccine development.

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“…The efficient antigen conjugation is critical for the hybridnanoparticle-based vaccine design. First, the stable lipid-polymeric nanoparticle can provide the conjugated antigen with a particulate nature, [36][37][38] leading to an improved recognition and capture by antigen presenting cells, as the immune system prefers to recognize particulate antigens rather than soluble protein antigens. 23,39,40 Second, the antigens (conjugated to nanoparticle surface) and molecular adjuvants (encapsulated within nanoparticles) could be codelivered to the same antigen presenting cells.…”

Section: Discussionmentioning

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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The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

Cited by 36 publications

References 66 publications

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose

Improving immunogenicity and safety of flagellin as vaccine carrier by high-density display on virus-like particle surface

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

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