Increased Efficacy of NKT Cell-Adjuvanted Peptide Vaccines Through Chemical Conjugation

Abstract

Through vaccination infectious diseases such as smallpox, polio, measles, and tetanus have either been eradicated or significantly restricted. However, there remain many diseases for which no effective vaccine exists, and therefore new vaccine approaches are still needed. Current vaccine approaches that generate strong immune responses are often based on ill-defined immunogens such as heat-killed or live-attenuated biological products that suffer from concerns related to safety, stability, and lengthy or complex manufacturing processes. For these reasons, there is a strong push toward vaccines that elicit immune responses to defined structures within the targeted pathogen or tissue, which can be achieved by injecting defined antigenic proteins or peptides. On their own, proteins or peptides are generally poorly immunogenic and they must be combined with immune stimulants known as adjuvants to drive antigen-specific immune responses. Recent studies have shown that the direct conjugation of adjuvant compounds to protein or peptide antigens can enhance the magnitude and quality of induced immune responses. In this chapter, we will discuss the chemical approaches our group has used to synthesize a new class of vaccines based on conjugation of peptides with lipid structures that activate innate-like T cells. The stimulatory milieu created by these structures helps drive potent T cell-mediated immune responses that can prevent infectious disease, or can act therapeutically in noncommunicable conditions as diverse as cancer and allergy.