Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain
Abstract
Vaccination against nicotine has been proposed as a potential treatment for nicotine dependence. Because vaccination may take months to elicit satisfactory antibody levels, the clinical usefulness of this approach will be enhanced if vaccination can be accomplished during continued nicotine intake (e.g., before a smoker quits). The current study examined the immunogenicity of a nicotine conjugate vaccine during continued nicotine dosing in rats, and its effects on nicotine distribution to brain. In the first experiment, nicotine was administered over 11 weeks as 20 intra venous (i.v.) bolus injections per day during the rat's active cycle to simulate the usual pattern of nicotine intake from cigarette smoking. In the second experiment, rats received a continuous s.c. infusion of nicotine by osmotic pump for 11 weeks to provide serum nicotine concentrations equivalent to those of a heavy smoker and 24 h/day nicotine exposure. Nicotine-specific antibody titers after the third booster dose were not compromised by either regimen of concurrent nicotine administration compared to those of rats receiving saline. A single additional i.v. nicotine dose was administered at the end of each experiment. The distribution of this single nicotine dose to brain was reduced by 40-60% in vaccinated rats compared to controls. Vaccine efficacy in reducing nicotine distribution to brain was not compromised by concurrent nicotine administration. These data suggest that vaccination during concurrent nicotine administration is feasible, and that the ability of vaccination to reduce nicotine distribution to brain is preserved even after months of nicotine dosing at rates approximating cigarette smoking.
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These results confirm other studies using non-inhalation routes of administration.
“These results confirm other studies using non-inhalation routes of administration [250–252].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [250]
With a 10-minute nose-only exposure modeling one cigarette, brain levels of nicotine were reduced by 90% in vaccinated animals.
“With a 10 minute nose-only exposure, modeling one cigarette, brain levels of nicotine were reduced by 90% in the vaccinated animals.”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [249]
After a 2-hour whole-body exposure to smoke, a 35% reduction in brain nicotine was detected in vaccinated animals.
“After a 2 hour whole body exposure to smoke, a 35% reduction in brain nicotine was detected [249].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [249]
After immunization using Pseudomonas exoprotein A conjugated to nicotine, rats exposed to cigarette smoke demonstrated a significant increase in serum nicotine levels, indicating prevention of nicotine entry into the brain.
“After immunization using Pseudomonas exoprotein A conjugated to nicotine, rats exposed to cigarette smoke demonstrated a significant increase in serum nicotine levels, indicating prevention of nicotine entry into the brain.”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [249]
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- Authors
- Hieda, Y., Keyler, D. E., Ennifar, S., Fattom, A., & Pentel, P. R.
- Affiliations
- Hennepin County Medical Center (US)
- Corresponding author
- Pentel, P.R
- Venue
- International Journal of Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 22
- Issue
- 10
- Pages
- 809-819
- ISSN
- 0192-0561 (ISSN-L)
- OpenAlex
- W2051268821
- Cited by
- 97
- References
- 25
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 1 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 8 · 2012: 5
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R01DA010714, DA10714)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- nicotine dependence, immunogenicity, osmotic pump, nicotine self-administration, smoking cessation
- MeSH terms
- Animals, Brain, Enzyme-Linked Immunosorbent Assay, Immunoglobulin E, Immunization, Injections, Subcutaneous, Nicotine, Radioimmunoassay, Vaccination, Nicotinic Agonists, Rats
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