A novel and efficient nicotine vaccine using nano-lipoplex as a delivery vehicle

A number of vaccines conjugating nicotine haptens with carrier proteins have been developed to combat nicotine caused tobacco dependence. Some vaccines, such as NicVAX, NicQb, advanced into clinical trials, but none of them were successful. Most of those vaccines have some innate disadvantages such as low nicotine loading capacity, easy degradation, and vulnerable to the clearance by reticulo-endothelial system (RES). Thus, there is undoubtedly an urgent need for developing novel vaccines against nicotine addiction. In this study, we assembled a liposome-protein based nanoparticle as a nicotine hapten delivery system. The nanoparticle (Scheme 1) was constructed by conjugating a model hapten carrier protein, bovine serum albumin (BSA), to cationic liposomes. This nano-sized complex, lipoplex, was characterized using zetasizer, transmission electron microscope (TEM), and flow cytometry. The efficacy of the lipoplex vaccine was evaluated in mice and compared with that of Nicotine-BSA conjugate (Nic-BSA). The lipoplex vaccine with Alum was able to elicit the highest NicAb titer of 11169±2112, which was significantly higher than that induced by either the vaccine without Alum or Nic-BSA with Alum. The significant immunostimulatory effect of this nano-lipoplex may provide a novel strategy to improve the immunogenic ability of current nicotine vaccines or other vaccines using small molecules as immunogens.