squalene and Disease-Models--Animal

Mollusk hemocyanins have been used for decades in immunological and clinical applications as natural, nontoxic, nonpathogenic, and nonspecific immunostimulants for the treatment of superficial bladder cancer, as carriers/adjuvants of tumor-associated antigens in cancer vaccine development and as adjuvants to dendritic cell-based immunotherapy, because these glycoproteins induce a bias towards Th1 immunity. Here, we analyzed the preclinical therapeutic potential of the traditional keyhole limpet hemocyanin (KLH) and two new hemocyanins from

Topics: Adjuvants, Immunologic; Alum Compounds; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Disease Models, Animal; Female; Hemocyanins; Immunity, Cellular; Immunity, Humoral; Immunotherapy; Mice; Mice, Inbred C57BL; Mollusca; Mouth Neoplasms; Polysorbates; Saponins; Squalene

Proteus mirabilis is a common pathogen in urinary tract infections (UTIs). There is no vaccine against P. mirabilis, thus a novel multi-peptide vaccine of MrpA, UcaA and Pta factors of P. mirabilis we designed and a mice model was used to evaluate its efficacy in combination with AddaVax adjuvant. According to the bioinformatics studies, 7 fragments of MrpA (31-75, 112-146), UcaA (68-117, 132-156) and Pta (210-265, 340-400, 496-570) with B and T cell epitope regions were selected for fusion construction. Mice subcutaneously vaccinated with the fusion MrpA.Pta.UcaA induced a significant increase in serum and mucosal IgG and IgA responses. The fusion also showed a significant induction in cellular responses (Th1 and Th2). The addition of AddaVax to fusion and the mixture of MrpA, UcaA, and Pta (MUP) improved the humoral and cellular responses, especially the IgG2a and IFN-γ (Th1 responses) levels. Fusion with and without AddaVax and MUP + AddaVax could maintain significant humoral responses until 6 months after the first vaccine dose. All vaccine combinations with and without adjuvant showed high effectiveness in the protection of the bladder and kidney against experimental UTI; this could be attributed to the significant humoral and cellular responses. The present study suggests that the AddaVax-based vaccine formulations especially the fusion Pta.MrpA.UcaA admixed with AddaVax as potential vaccine candidates for protection against P. mirabilis. Furthermore, AddaVax could be considered as an effective adjuvant in designing other vaccines against UTI pathogens.

Topics: Adjuvants, Immunologic; Animals; Bacterial Vaccines; Disease Models, Animal; Mice; Polysorbates; Proteus Infections; Proteus mirabilis; Squalene; Urinary Tract Infections; Vaccines, Subunit