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Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response

Author:
Awasthi, Shanjana, Vilekar, Prachi, Conkleton, Alexandra, Rahman, Negar
Source:
Vaccine 2019 v.37 no.12 pp. 1685-1691
ISSN:
0264-410X
Subject:
Coccidioides, albumins, animal models, blood sampling, blood serum, cell-mediated immunity, coccidioidomycosis, dendritic cells, epitopes, fungi, immune response, immunization, immunoglobulin G, interferon-gamma, interleukin-17, lactic acid, lungs, lymph nodes, mice, necropsy, pathogens, plasmids, vaccine development, vaccines, virulence
Abstract:
Valley Fever, or coccidioidomycosis, is caused by a soil-borne, highly virulent fungal pathogen, Coccidioides spp. Infection with Coccidioides can be life-threatening. Since an effective treatment is not available and the T cell-mediated immune response is protective, vaccine development is of interest. In this study, a primary dendritic cell (DC)-vaccine was evaluated for its ability to stimulate Coccidioides antigen-specific immune response in an extremely susceptible BALB/c mouse model. The DC-vaccine (Ag2-DC) was prepared by non-virally transfecting the primary bone marrow-derived DCs with a plasmid DNA encoding Ag2/PRA (protective epitope of Coccidioides). Mice were intranasally immunized with Ag2-DC on days 2 and 10. Immunized mice were necropsied on days 8, 32, and 44. Major organs and blood samples were harvested. The most common indicators of injury (protein, lactate, and albumin), Ag/PRA-specific cytokine-secreting cells, and IgG and its isotypes were determined by biochemical and immunologic assays, respectively. No signs of sickness were noted. Similarly, no significant changes were observed in the levels of total lung protein, lactate, and albumin, in immunized mice compared with healthy control mice. Interferon (IFN-γ), and interleukin (IL)-4 and IL-17 cytokine-secreting cells were observed in lung and lymph nodes upon Ag2-DC immunization. Our results showed that the levels of serum IgG and its isotypes were increased in Ag2-DC-immunized mice. This report provides evidence of DC immunization-stimulated Ag2/PRA-specific immune responses.
Agid:
6295469