Novel Vaccine Adjuvants

Vaccines still remain the most successful method for protection and eradication against diseases. However, to avoid harmful effects associated with whole organism vaccines, new vaccine candidates are composed of parts of an organism, and therefore these are weakly immunogenic. Adjuvants are essential components of vaccines that nonspecifically stimulate the immune system, particularly the innate immune system cells, to enhance the immunogenicity of vaccines. Initially the major function of adjuvants such as alum was to allow sustained presence of antigens by preventing their degradation in vivo. Recent advances have, however, demonstrated that success of alum as an adjuvant is also due to its ability to activate the innate immune system cells. Significant progress in the last decade has increased our understanding of the innate immune system which is highly complex and can be activated via a wide array of receptors to generate different immune responses. The nature of adaptive immune response, quality, and quantity are governed by how the innate immune responses are activated. Novel adjuvants are therefore targeted to receptors expressed on antigen-presenting cells (APCs) such as dendritic cells (DCs) to activate the innate immune system. DCs express an array of pathogen recognition receptors (PRRs) so that they can recognize any threat to the body. Examples of PRRs include the TLRs, CLRs, and NLRs. Apart from preventing infections, vaccinations are also being used as therapy against tumors. Targeting antigens to APCs along with adjuvants allows the induction of immune response against tumors. The manuscript by L. Arribillaga et al., in this tissue, demonstrates that fusion of an antigen to the extra domain A from fibronectin (EDA) targets antigens to TLR4-expressing cells such as DCs leading to their activation. The approach is also effective for cross-presentation as well as the induction of antiviral/tumor immunity. Furthermore, the approach is universal as conjugation of EDA to streptavidin allows any biotinylated antigens to be used as immunogen for vaccination purposes. In contrast to the approach above, N. Kojima et al. use oligomannose-coated liposomes to target and stimulate APCs. The oligomannose on the liposomes targets antigens to the C-type lectin receptor (CLR) and is effective in inducing CTLs and/or Th1 cells. This approach is also universal because both lipophilic and hydrophilic antigens can be incorporated in the liposomes. Contrary to these surface receptor targeting methodologies, C. A. Colaco et al. discuss the merits of using heat shock proteins (HSPs) as vaccine adjuvants because HSPs are …