Category: Clinical Pharmacology
Purpose: The purpose of this study is to test the feasibility of using a nasal nicotine vaccine candidate to induce nicotine-neutralizing antibodies not only in the blood, but also in the lung and nasal mucosal secretions. Anti-nicotine antibodies in the lung mucosal secretion are expected to reduce nicotine absorption from cigarette smoking.
Methods: Nicotine was chemically conjugated to keyhole limpet hemocyanin (KLH) protein using carbodiimide conjugation reaction. The resultant antigen (i.e. Nic-KLH) was admixed with an adjuvant (Adj) in phosphate-buffered saline (PBS) and nasally administered to BALB/c mice, two week apart, for three times. One month following the last immunization, mice were euthanized to collect serum samples as well as nasal wash and lung lavage. Anti-nicotine IgG and IgA titers and the affinity and specificity of the antibodies were measured using ELISA.
Results: Nasal immunization with Nic-KLH/Adj induced anti-nicotine IgG in mice, to a level comparable to that in mice subcutaneously injected with Nic-KLH/Adj. However, anti-nicotine sIgA response was only induced in mice nasally dosed with Nic-KLH/Adj, not in mice subcutaneously injected with Nic-KLH/Adj (Fig. 1). Competitive ELISA assay reveals that the anti-nicotine antibodies were able to neutralize nicotine. Additionally, anti-nicotine antibodies in the serum bind specifically to nicotine, but not to acetylcholine, the endogenous neurotransmitter, nor cotinine, the primary nicotine metabolite.
Conclusion: Nasal nicotine vaccine induced a high level of nicotine-specific neutralizing antibodies in the blood and the lung and nasal mucosal secretions. Anti-nicotine antibodies in the respiratory mucosal secretions may help to reduce nicotine absorption form cigarette smoking