A novel nanovaccine against nicotine addiction smoking is a growing global problem. Chronic use of tobacco is considered a responsible factor for serious diseases such as chronic obstructive pulmonary disease, stroke, chronic lung disease, and cancer. There are more than 60 million smokers in the U.S alone. Despite the urgent need, finding ways to combat the problem has been a constant challenge to the society and the medical field. Current pharmacological therapies have shown very limited success with some serious side-effects, such as depression with suicidal behavior. On the other hand, immunopharmacotherapy or vaccination has emerged as a promising alternative. However, all current vaccines have shown limited efficacy, and thus there is undoubtedly a strong need for improved nicotine vaccines. In this project, building on the tremendous success of a proof-of-concept study (R21DA030083), we propose to synthesize biodegradable nanoparticle based novel nanovaccines against nicotine. Different from all nicotine vaccines that have gone through clinical trials, our nanovaccines will be constructed by assembling lipids around biodegradable nanoparticles, and the carrier proteins with conjugated haptens will be conjugated to the lipids. The innovation of this project involves the use of the biodegradable nanoparticle, immune enhancing lipids, specifically selected carrier proteins, and a molecular adjuvant in the assembly of the nanovaccines. We expect that, through successfully executing the carefully designed experiments, we will be able to identify a leading vaccine candidate that will show unprecedentedly high antibody titers against nicotine and can be advanced into clinical trials. The investigators, with superbly synergizing expertise, are committed to the success of this project. The broad impact of this project resides in the potential of a new and effective vaccine against nicotine, its potential social and economic impact, and a platform technology for producing much needed vaccines against other psychoactive drugs. Our goal is to develop an effective vaccine with controlled size that can elicit strong specific immune response toward nicotine and can be subsequently advanced to clinical trials. To achieve the goal, the following specific aims are proposed: 1) preparation of PLGA nanoparticles, 2) assembly of nanovaccine particles, and 3) evaluation of the immunogenicity and biosafety of the vaccines. With the strong and supportive preliminary results and the collective experiences of the investigators, we strongly believe this project will be extremely successful and eventually lead to the emergence of an effective vaccine against nicotine addiction.

Public Health Relevance

Smoking can cause various devastating diseases. There is an urgent need for developing highly effective vaccines against nicotine addiction. This project will attempt to develop novel biodegradable nanovaccines for the treatment of nicotine addiction, and, if successful, it will have a significant impact on smoking cessation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DA036850-02
Application #
8877473
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Chiang, Nora
Project Start
2014-07-01
Project End
2017-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Virginia Polytechnic Institute and State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24060
Zhao, Zongmin; Harris, Brian; Hu, Yun et al. (2018) Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction. Biomaterials 155:165-175
Hu, Yun; Zhao, Zongmin; Harmon, Theresa et al. (2018) Paradox of PEGylation in fabricating hybrid nanoparticle-based nicotine vaccines. Biomaterials 182:72-81
Lou, Song; Zhao, Zongmin; Dezort, Micah et al. (2018) Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer. ACS Omega 3:9210-9219
Zhao, Zongmin; Hu, Yun; Harmon, Theresa et al. (2017) Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization. Biomaterials 138:46-56
Zhao, Zongmin; Powers, Kristen; Hu, Yun et al. (2017) Engineering of a hybrid nanoparticle-based nicotine nanovaccine as a next-generation immunotherapeutic strategy against nicotine addiction: A focus on hapten density. Biomaterials 123:107-117
Zhao, Zongmin; Hu, Yun; Hoerle, Reece et al. (2017) A nanoparticle-based nicotine vaccine and the influence of particle size on its immunogenicity and efficacy. Nanomedicine 13:443-454
Zhao, Zongmin; Lou, Song; Hu, Yun et al. (2017) A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled Multidrug Delivery. Mol Pharm 14:2697-2710
Hu, Yun; Smith, Daniel; Frazier, Evan et al. (2016) The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine. Biomaterials 106:228-39
Babahosseini, Hesam; Srinivasaraghavan, Vaishnavi; Zhao, Zongmin et al. (2016) The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells. Lab Chip 16:188-98
Saylor, Kyle; Zhang, Chenming (2016) A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Toxicol Appl Pharmacol 307:150-164

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