Journal of Vaccine Research 2024, Vol.14, No.2, 65-75 http://medscipublisher.com/index.php/jvr 66 2 Mechanisms of Adjuvants Adjuvants are critical components in vaccine formulations, particularly in cancer vaccines, as they enhance the body's immune response to the presented antigens. They work through various mechanisms, including the activation of innate immune responses, enhancement of antigen presentation, and modulation of the tumor microenvironment. 2.1 Enhancing immune response Adjuvants enhance the immune response by stimulating antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. This activation leads to the production of cytokines and chemokines, which are crucial for the recruitment and activation of other immune cells, including T cells and B cells. For instance, the use of Toll-like receptor (TLR) agonists as adjuvants has been shown to significantly enhance cytokine secretion and improve antigen presentation, leading to robust cytotoxic T lymphocyte (CTL) responses (Kim et al., 2018; Chávez et al., 2020; Kocabaş et al., 2020; Luchner et al., 2021). 2.2 Types of adjuvants Various types of adjuvants are used in cancer vaccine development, each with unique properties and mechanisms of action. The following sections discuss some of the most commonly used adjuvants. 2.2.1Alum Aluminum-based adjuvants, commonly referred to as alum, are among the oldest and most widely used adjuvants. They primarily enhance the immune response by promoting the uptake of antigens by APCs and stimulating the production of pro-inflammatory cytokines. Alum has been shown to be effective in enhancing humoral immunity, although its ability to stimulate cellular immunity is limited (Gonzalez-Lopez et al., 2019; Lee and Suresh, 2022). 2.2.2 Oil-in-water emulsions Oil-in-water emulsions, such as MF59, are another class of adjuvants that have been used to enhance vaccine efficacy. These emulsions work by creating a depot effect at the injection site, which allows for a sustained release of the antigen. This prolonged exposure helps in the activation of APCs and the subsequent induction of both humoral and cellular immune responses (Lee and Suresh, 2022). 2.2.3 Toll-like receptor (TLR) agonists TLR agonists are a promising class of adjuvants that target specific TLRs on immune cells, leading to the activation of innate immune responses. TLR agonists can be classified into cell surface TLRs (e.g., TLR1, TLR2, TLR4) and intracellular TLRs (e.g., TLR3, TLR7, TLR9). These adjuvants have been shown to enhance the production of pro-inflammatory cytokines and improve antigen presentation, thereby boosting both humoral and cellular immunity. For example, TLR3 agonists have been associated with extended survival in glioma patients when used in conjunction with dendritic cell vaccination (Antonios et al., 2020; Chávez et al., 2020; Luchner et al., 2021). 2.2.4 Saponins Saponins are natural glycosides that have been used as adjuvants due to their ability to stimulate strong immune responses. They work by forming complexes with cholesterol in cell membranes, leading to the formation of pores that enhance antigen uptake by APCs. Saponin-based adjuvants, such as QS-21, have been shown to induce robust CTL responses and are being investigated for their potential in cancer vaccines (Lee and Suresh, 2022). 2.2.5 Cytokines and chemokines Cytokines and chemokines are signaling molecules that play a crucial role in the regulation of immune responses. As adjuvants, they can be used to modulate the tumor microenvironment and enhance the recruitment and activation of immune cells. For instance, the use of cytokines such as interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to improve the efficacy of cancer vaccines by promoting the activation and proliferation of T cells (Kocabaş et al., 2020).
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