Vaccine Adjuvant
a technology of adjuvants and vaccines, applied in the field of vaccine adjuvants, can solve the problems of limited knowledge, relative genetic complexity and intractability, and the development of safe and effective vaccines against fungi has been a major hurdl
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[0109]Adaptive immunity is critical for the prevention and resolution of fungal infections. The contribution of antibodies to host defense is debated. In contrast, Ag-specific CD4+ T cells play the major role in fungal resistance, as evidenced by the high incidence of life-threatening fungal infections in patients with impaired CD4+ T cells. CD4+ T cells confer resistance by secretion of T-helper 1 (Th1) and Th17 cytokines such as IFN-γ, TNF-α, GM-CSF, and IL-17A, which activate neutrophils, monocytes, macrophages and DCs for fungal clearance. Since CD4+ T cells are germane to host defense against fungi, the challenge is how best to elicit these T cells.
[0110]The transition from innate to adaptive immunity is fostered by dendritic cells (DCs). These cells process and present Ag to naïve CD4+ T cells in the context of co-stimulatory factors (e.g. cell surface ligands and cytokines) that provide the combination of signals necessary to induce naive T cell activation and proliferation. ...
example 2
[0169]The embodiment described herein demonstrates the use of Bl-Eng2 as a vaccine adjuvant in bacterial and viral vaccines. As demonstrated in FIG. 12 and FIG. 13, Bl-Eng2 functions as an adjuvant in bacterial and viral vaccine formulations and increased the number of activated (CD44+) CD4+ and CD8+ producing T cells. Mice were vaccinated with Ag85B from Mycobacterium tuberculosis and Nucleoprotein (NP) from Influenza A in the presence and absence of Bl-Eng-2 and compared the number of corresponding cytokine producing CD4+ and CD8+ T cells, respectively. In the TB vaccine model, Ag-specific IL-17 and IFN-γ producing CD4+ T cells and in the Influenza model, IFN-γ producing cytotoxic CD8+ T cells (CTL) are thought to be most protective against bacterial and viral infection, respectively. The addition of Bl-Eng-2 to Ags 85B or NP augmented the number of cytokine producing Ag-specific CD4+ and CD8+ T cells in both models. Thus, Bl-Eng-2 augments immunity also in response to non-fungal ...
example 3
[0170]The embodiment described herein demonstrates the use of Bl-Eng2 as a novel antigen for use in vaccine compositions. As demonstrated in FIGS. 14A-14B and FIGS. 15A-15B, Bl-Eng2 functions as an antigen when used in vaccine compositions to raise antifungal T cells in the subject mice. Mice subcutaneously vaccinated with Bl-Eng2 formulated in IFA had significantly reduced lung CFU at 4 (15-fold) and 11 post-infection (>5,000 fold) compared to control mice (FIG. 14). Splenocytes from Bl-Eng2 vaccinated mice produced >10 ng / ml INF-γ when stimulated in vitro with full length Bl-Eng2 protein or peptide 1 which is comprised of the following amino acid sequence: AFFDGPDPSNAYV (SEQ ID NO:4). Therefore vaccination with this peptide alone will engender a similar level of protection as full length Bl-Eng2 protein.
[0171]This peptide could also be used to expand autologous, endogenous Bl-Eng2-specific T cells of patients that will undergo transplantation, chemotherapy or other immunocompromis...
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