New-age vaccine adjuvants, their development, and future perspective

Abstract

In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.

Keywords: adjuvants; immune response; improved vaccines; infectious disease; mucosal vaccine.

Figure 1

Schematic representation of vaccine adjuvants and their benefits.

Figure 2

MF59 adjuvant and its mechanism of action. At the injection site, MF59 adjuvant-activated macrophages secrete the chemokines that stimulate and recruit the immune cells. Differentiation converts immune cells into antigen-presenting cells to activate B and T cells to impart strong humoral and cellular immune responses.

Figure 3

Mechanism of action of the dmLT adjuvant. (I) At the vaccination site, the dmLT adjuvant stimulates the innate immune response and activated epithelial cells secrete IL-8 and G-CSF. (II) Dendritic cells (DCs) are activated and recruited at the injection site where they process and present the antigen. It also upregulates the costimulatory molecules, i.e., CD80 and CD86, and stimulates the expression of IL-1, IL-6, IL-23, and G-CSF. (III) The activated DCs migrate to secondary lymphoid organs where they stimulate the differentiation of antibody-secreting plasma B cells and the generation of antigen-specific Th cells. Overall, a strong Th17 immune response is imparted. Th17 cells are identified as essential in immunity and in stimulating germinal center formation in secondary lymphoid organs as well as in enhancing IgA secretion.