Toll-like Receptor 9 Agonists as Adjuvants for Nanoparticle-Based Nicotine Vaccine

Mol Pharm. 2021 Mar 1;18(3):1293-1304. doi: 10.1021/acs.molpharmaceut.0c01153. Epub 2021 Jan 26.


Nicotine vaccine was considered a promising therapy against smoking addiction. The level of immune response that a nicotine vaccine can induce is pivotal to its efficacy. In this study, Toll-like receptor 9 agonists, namely, CpG ODN 1555 and CpG ODN 1826, were incorporated into a nanoparticle-based nicotine vaccine (NanoNicVac) to enhance its immunogenicity. The results showed that NanoNicVac containing either CpG ODN 1555 or CpG ODN 1826 could be rapidly internalized by dendritic cells. In mice trials, it was found that NanoNicVac with CpG ODN 1555 and CpG ODN 1826 induced 3.3- and 3.2-fold higher anti-nicotine antibody titer than that by the native NanoNicVac after two injections, respectively. Instead of enhancing the immunogenicity of the vaccine, however, mixtures of the two CpG ODNs were observed to exert an immune-suppressing effect on NanoNicVac. Finally, the histopathological examination on major organs of the mice immunized with the NanoNicVacs proved that NanoNicVac with either CpG ODN 1555 or CpG ODN 1826 as adjuvants did not cause detectable toxicity to the mice.

Keywords: CpG ODN; adjuvant; hybrid nanoparticle; nicotine vaccine; smoking cessation.

Publication types

  • Research Support, N.I.H., Extramural