Adjuvants for Substance Abuse Vaccines

Abstract

Small molecules are unable to stimulate the immune system by themselves, and so require conjugation to a larger structure, i.e., a carrier molecule (often a protein) to enable effective engagement of immune cell receptors that can initiate adaptive immune responses. However, in most circumstances, the molecular structure of the hapten and a protein carrier molecule alone are inadequate to elicit a strong immune response. Since blocking the pharmacological effects of substance abuse drugs requires binding of a large fraction of the drug molecules, robust antibody responses are essential for drugs that are active in the high nanomolar or low micromolar range. To achieve such high specific antibody levels, vaccine formulations must have additional costimulatory signals in order to ramp up the immune responses. The costimulatory signals are most often provided by added materials that are generally called adjuvants. While the field has become markedly better understood and more complex than when the early adjuvants were described by Charles Janeway as the “immunologists’ dirty little secret,” the fundamental issues involved remain the same – stimulating antigen-presenting cells, activating helper T cells, and activating B cells in order to promote differentiation, proliferation, and high-level specific immune responses. Each of these steps is now understood to involve multiple molecular signals and pathways both inside and outside each cell type, resulting in an elegant and flexible, though incredibly complex, regulated immune response.