Project Lead(s): Hoang-Thanh Le
Issue
According to World Health Organization statistics, tobacco is a global pandemic that results in six million deaths per year. Smoking is responsible for 30% of all cancer-related deaths and 85% of all lung cancers, in addition to being linked to cardiovascular disease and overall decreased health.
Effective intranasal vaccines against nicotine require potent but safe mucosal adjuvants to enhance specific antibody production and avoid the development of antigen tolerance.
Solution
An intranasal vaccine is being developed using a novel adjuvant delivery system that can stimulate mucosal immunity and can serve as a first line of defence to block nicotine inhaled and absorbed from cigarettes before it reaches the bloodstream.
Using a novel peptide/bacterial derived adjuvant particle platform that stimulates IL-1β production, a potent mechanism for mucosal immunity, the team will convert nicotine into an immunogenic compound that can be administered intranasally. This safe system generates not only highly selective anti-nicotine IgG antibodies in the blood but also produces anti-nicotine IgA and IgG in the respiratory tract. These antibodies can rapidly bind nicotine inhaled from cigarettes in the lung tissue before it reaches the bloodstream and prevent it from reaching the brain, where it exerts its effect.
The approach has been tested in collaboration with the Pasteur Institute of Ho Chi Minh City in Vietnam.
Outcome
Preliminary tests, using mice challenged with radioactive [3H]-nicotine, showed that anti-nicotine antibodies produced in vaccinated mice can block nicotine from reaching the brain, as brain nicotine levels in vaccinated mice were four times lower than in non-vaccinated controls and pulmonary nicotine levels in vaccinated mice are higher than in non-vaccinated controls.
After four animal experiments, results indicated that anti-nicotine IgG titers of 106 could be reached in vaccinated mice, which were sustained for 16 months following the final vaccination.
In addition, the vaccine candidate induces mucosal IgA and IgG in bronchoaveolar lavages (BAL) and in distal mucosa. These antibodies are essential as a first line of defence in neutralizing nicotine.
Moreover, the vaccine does not promote an allergic response, as no anti-nicotine IgE was detected in the sera of vaccinated mice.
Preliminary data from histopathological analyses of tissues indicated that the vaccine did not appear to be toxic to vaccinated rats and induced plasma cells in the lung, as compared to the control. These tests were performed in Vietnam.
The team also demonstrated that the conjugate nicotine vaccine was able to induce humoral and systemic immunological memory against nicotine.
This vaccine is produced as a freeze-dried formulation that facilitates the transport and storage at room temperature. This is advantageous, as it results in low cost production of the vaccine, which is beneficial for developing countries.
This needle-free platform can also be employed to develop other vaccines for drug addiction treatments related to cocaine, methamphetamine and heroin.
With these promising results, the project team plans to optimize and improve the production of the vaccine to make it ready for pre-clinical and eventually human trials.
Knowledge was widely disseminated in conference presentations and publications.
The Northern Cancer Foundation awarded a grant of $230,000 to support four years’ work on the project.