Intranasal delivery of a nicotine vaccine candidate induces antibodies in mouse blood and lung mucosal secretions that specifically neutralize nicotine

Abstract

Objective

Cigarette smoking is one of the leading causes of death in the world. The majority of the smokers have tried to quit, but only a few of them were able to achieve long-term abstinence, due to the high addictiveness of nicotine. Nicotine-specific antibodies have the potential to block the euphoric effect of nicotine by forming antibody-antigen complexes in the blood circulation. Since nicotine is taken largely by inhalation, inducing anti-nicotine antibodies in lung and nasal mucosal secretions, in addition to blood circulation, is expected to be beneficial.

Significance

The importance of this study is to establish the feasibility of inducing nicotine-neutralizing antibodies not only in the blood, but also in the lung and nasal mucosal secretions, by intranasal administration of a nicotine vaccine candidate.

Methods

Nicotine-keyhole limpet hemocyanin conjugate (Nic-KLH) was prepared and mixed with monophosphoryl lipid A (MPL) as an adjuvant. Nic-KLH/MPL was given intranasally or subcutaneously to mice, and the titers, affinity, and specificity of the nicotine-specific antibodies in nasal and lung mucosal secretions and blood samples were determined using (competitive) ELISA.

Results

Nasal Nic-KLH/MPL immunization elicited robust nicotine-specific neutralizing IgA in mouse nasal and lung secretions, in additional to anti-nicotine IgG in blood circulation. The nicotine-specific IgG level in mice nasally immunized with Nic-KLH/MPL was lower than in mice subcutaneously immunized with the same Nic-KLH/MPL, but a heterologous prime-boost immunization strategy helped to increase it.

Conclusion

Intranasal immunization with a nicotine vaccine candidate can induce systemic and mucosal antibodies that specifically neutralize nicotine.

Keywords:

• Vaccine
• intranasal
• mucosal
• neutralizing antibody
• heterologous

Acknowledgments

This work was supported in part by the Alfred and Dorothy Mannino Fellowship in Pharmacy at UT Austin. R.F.A. was supported in part by a scholarship from the King Saud University. S.A.V. was supported in part by the Becas-Chile Scholarship from the Government of Chile.

Disclosure statement

No potential conflict of interest was reported by the author(s).