Nicotine nanovaccines and uses thereof
Inventors
Zhang, Chenming • Zhao, Zongmin • HU, Yun
Assignees
Virginia Tech Intellectual Properties Inc • Virginia Polytechnic Institute and State University
Publication Number
US-11278608-B2
Publication Date
2022-03-22
Expiration Date
2037-01-05
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Abstract
Provided herein are nicotine polymer-stabilized nanoparticles, formulations thereof, and vaccines. Also provided herein are methods of treating and/or preventing nicotine addiction in a subject in need thereof.
Core Innovation
The invention relates to nicotine polymer-stabilized nanoparticles, specifically hybrid lipid-polymeric nanoparticles with a core-shell structure for use as vaccines and formulations to treat or prevent nicotine addiction. These nanoparticles feature a polymer core (e.g., poly(lactic-co-glycolic acid)) encapsulated by a lipid shell, to which two distinct nicotine-hapten antigens are conjugated—one attached to a stimulating protein (such as KLH, TT, CRM197, or BSA) and another directly to the outer surface of the lipid shell, not linked to a stimulating protein. This architecture enables targeted antigen presentation to the immune system.
The problem addressed is the high failure rate of existing therapies for nicotine addiction, including mental health and nicotine replacement therapies as well as traditional conjugate nicotine vaccines. Previous conjugate vaccines suffer from fast degradation, low nicotine loading, poor immune cell uptake, and low bioavailability, which limit their immunogenicity and effectiveness for smoking cessation. Even recently developed nanoparticle-based vaccines have not generated sufficient immunogenicity or clinical efficacy.
The innovation solves these problems by designing lipid-polymeric nanoparticles capable of displaying multiple nicotine-hapten molecules localized at different sites (both on stimulating proteins and directly on the lipid shell), thereby enhancing immune recognition and response. The nanoparticles facilitate efficient cellular uptake and processing by immune cells such as dendritic cells, enable flexible inclusion of various adjuvants (including TLR agonists), and can be tuned for hapten density and particle size. This leads to improved immunogenicity, antibody production, and pharmacokinetic effectiveness in blocking nicotine from entering the brain.
Claims Coverage
The patent includes three independent claims covering the composition of nicotine lipid-polymeric nanoparticles, vaccine formulations utilizing these nanoparticles, and methods of treating nicotine addiction using the nanoparticles.
Lipid-polymeric nanoparticle with dual nicotine-hapten localization
A nanoparticle comprising: - A polymer core; - A lipid shell encapsulating the core, with the shell comprising a lipid bilayer including dioleoyl trimethylammonium propane (DOTAP) or its derivative, DSPE-PEG-maleimide, and cholesterol; - A first stimulating molecule attached to the surface of the lipid shell; - A first nicotine-hapten antigen attached to the first stimulating molecule; - A second nicotine-hapten antigen attached directly to the outer surface of the lipid shell and not to the stimulating molecule; - Optionally, a second stimulating molecule located in a range of locations including within or attached to the polymer core, encapsulated in or attached to the lipid shell (either inner or outer surface), or combinations thereof.
Vaccine formulation containing the defined nanoparticle and pharmaceutically acceptable carrier
A vaccine formulation comprising: - The patented nanoparticle described above, - And a pharmaceutically acceptable carrier.
Method to treat nicotine addiction by administering the nanoparticle
A method of treating nicotine addiction or a symptom thereof by administering the above-defined nanoparticle to a subject in need thereof.
In summary, the claims establish broad protection for the structure and composition of nicotine lipid-polymeric nanoparticles with distinct hapten and protein configurations, the use of such nanoparticles in vaccine formulations, and method claims for their use in treating or preventing nicotine addiction.
Stated Advantages
The nicotine lipid-polymeric nanoparticles provide increased immunogenicity as compared to current conjugate and nanoparticle-based nicotine vaccines.
They induce a lower anti-stimulating protein antibody response, offering improved specificity for nicotine.
They produce a more Th2-skewed immune response, which is desirable for effective antibody-mediated neutralization of nicotine.
Formulated nanoparticles show enhanced recognition and uptake by immune cells, particularly dendritic cells.
The nanoparticles can be engineered for controlled hapten density and particle size, optimizing immune responses and pharmacokinetic efficacy.
Delivery system permits efficient co-delivery of antigens with adjuvants, including molecular adjuvants such as MPLA and CpG oligodeoxynucleotides.
Vaccine formulations show improved ability to retain nicotine in serum and block its entry into the brain in animal models.
Demonstrated relative safety with no detectable histopathological lesions in major organs of immunized mice.
Documented Applications
Methods of treating and/or preventing nicotine addiction in subjects in need thereof by administration of the described nanoparticle or vaccine formulation.
Use in the manufacture of medicaments for treatment or prevention of nicotine addiction.
Inducing immune responses, particularly B cell responses specific to nicotine, for the purpose of generating anti-nicotine antibodies.
Blocking or reducing entry of nicotine into the brain, thereby mitigating addiction-relevant pharmacological effects.
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