Mast cell activators: a new class of highly effective vaccine adjuvants

Abstract

Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, we demonstrate that subcutaneous or nasal administration of small-molecule MC activators with vaccine antigens evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. These responses were MC dependent and correlated with increased dendritic cell and lymphocyte recruitment to draining lymph nodes. Nasal instillation of these formulations also evoked antigen-specific secretory IgA and provided protection against anthrax lethal toxin challenge in vitro and against vaccinia virus infection in vivo. Collectively, these results define the MC as an integral sensory arm of the adaptive immune system. Moreover, they highlight MC activators as a new class of vaccine adjuvants, capable of inducing protective antigen-specific immune responses through needle-free routes of administration.

Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

“…Although studies are needed on the role of MCs in generation of Agspecific immunity, the studies reported here show that MCs have a role in the effect of IL-18 as an adjuvant and in augmentation of the CTL response induced by IL-33 as a nasal vaccine adjuvant. MC activators (e.g., compound 48/80) have been reported to stimulate protective immune responses against infections (28,32). In addition, these immune responses are correlated with DC trafficking and lymphocyte recruitment to draining lymph nodes (DLN).…”

Cross-protection against influenza virus infection by intranasal administration of nucleoprotein-based vaccine with compound 48/80 adjuvant

“…11 Therefore, recently, people have started to study the efficacy of MC activator C48/80 as an adjuvant, and C48/80 has been shown to be a potential mucosal adjuvant. Just like other mucosal adjuvants, C48/80 as a nontoxic nasal adjuvant 12 can also induce effective sIgA at the mucosal location, and clear the virus in the early stage of pathogen invasion, playing an immunological effect. However, up to now, the mechanism of action of C48/80 adjuvant has not been fully explored, and the related reports on C48/80 as an adjuvant in influenza vaccine were also very few.…”

“…In addition, C48/80 has also been confirmed as a nontoxic nasal adjuvant. 12 In this study, the NP protein was expressed using E. coli expression system and then purified as a subunit vaccine, and was immunized intranasally to mice in combination with C48/80 adjuvant. It was found that NP, as a candidate vaccine, could protect mice against the influenza virus challenge, and that C48/ 80 adjuvant could significantly enhance the protective effect of the NP vaccine.…”

Antitumor effect and immune response induced by local hyperthermia in B16 murine melanoma: Effect of thermal dose

“…Local hyperthermia increased the infiltration of leukocytes, including mast cells at the site of tumors (27). The adjuvant activity of C48/80 was associated with its ability to induce DC migration via a mechanism that required mast cells and mast cell-derived TNF (14). Furthermore, McGowen et al reported that C48/80 produced much greater levels of IFN than it did IL-4, IL-5, IL-6 or IL-17, and reduced the IgG1/IgG2a ratio.…”

“…Compound 48/80 (C48/80) is a stimulus of mast cell degranulation (12,13). It has been reported that the mast cell activator C48/80 was an effective and safe adjuvant for the induction of anthrax lethal toxin neutralizing antibody responses when delivered intranasally, intradermally or via the footpad to mice with anthrax protective antigen (13,14). However, few studies were found concerning the use of C48/80 in tumor treatment; therefore, in the present study, local hyperthermia combined with C48/80 was applied for melanoma lung metastasis treatment.…”