Another advantage is that the TCC can be conjugated with the nicotine hapten in situ during solid phase synthesis, whereas recombinant protein conjugation produces a more heterogeneous product requiring a more complicated purification and scale-up process. The superiority of synthetic carrier manufacturing becomes even more apparent for production of a multivalent vaccine, where again, multiple TCC-based antigens could be produced reproducibly during a single round of synthesis, while a multivalent recombinant vaccine would require development of multiple independent conjugation, purification, and confirmation procedures, which magnifies the time and costs even further. Vaccine adjuvants control the magnitude and quality of adaptive T and B cell responses by facilitating AZD2281 antigen uptake into antigen presenting cells and stimulating innate pathways that control leukocyte recruitment to the site of injection. To date, the only adjuvant used in clinical nicotine vaccine studies has been Alum, however numerous studies suggests that Alum may be relatively weak in comparison to adjuvants that target innate pattern recognition receptors on APC. The receptor that binds bacterial LPS, TLR-4, plays a critical role in CD4 T cell regulation of germinal center formation, affinity maturation, and the production of long-lived antibody-secreting plasma cells, and we have shown previously that adjuvants formulated with the synthetic TLR-4 ligand, GLA, are potent stimulators of protective T-cell mediated antibody responses against heterosubtypic H5N1 influenza viruses. Here we learned that, relative to an Alum adjuvant, GLA-SE played a major role in regulating higher Ab titers, improved Ab affinities, and a significant increase in functional inhibitor activity. The observation that GLA-mediated antibody responses were larger and more consistent with TCCnic-12 than KLHnic-22 may result from the placement of 2 dominant H2Db restricted helper T-cell epitopes within each monomer of the TCC. In summary, we have developed two important tools that could significantly improve the performance of anti-addiction vaccines in people. The first is a novel synthetic hapten carrier and the second is the adjuvant GLA-SE, which was far superior to Alum in augmenting anti-nicotine Ab titer, affinity, and function. This is consistent with previous work showing that addition of the TLR9 ligand CpG to Alum significantly improved functional nicotine antibody responses in both mice and Cynomolgus monkeys. Fossil energy is a finite, non-renewable resource that has significant impact on the world economy. Current world-wide, energy consumption is around 1306108 t coal equivalent per year, of which fossil energy comprises over 80%. Energy demand and consumption is expected to increase as a function of both world economy and population growth. Spot shortages of fossil energy commonly occur and the increased utilization of fossil fuels suggests it is reasonable to predict future depletion of fossil energy throughout the world. Moreover, utilization of fossil energy results in SO2, CO, and CO2 emissions, which are believed to contribute to climate change.