Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response. Issue 12 (14th March 2019)

• Record Type: Journal Article
• Authors: Awasthi, Shanjana; Vilekar, Prachi; Conkleton, Alexandra; Rahman, Negar
• Is Part Of: Vaccine. Volume 37:Issue 12(2019)
• Page Start: 1685
• Page End: 1691
• Publication Date: 2019-03-14
• Subjects: Dendritic cells -- Vaccination -- Coccidioides -- Immune response; Ag2/PRA Antigen 2/Proline rich antigen -- Ag2-DC Dendritic cells transfected with a plasmid DNA encoding Ag2/PRA -- ANOVA Analysis of variance -- 1% BSA-TBST 1% bovine serum albumin in Tris-buffered saline containing 0.05% Tween 20 -- DC Dendritic cells -- DMEM Dulbecco's minimum essential medium -- ELISA Enzyme-linked immunosorbent assay -- ELISPOT Enzyme-linked immunospot assay -- EDTA Ethylenediamine tetraacetic acid -- GM-CSF Granulocyte macrophage colony stimulating factor -- HEPES 2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid -- IFN-γ Interferon gamma -- IgG Immunoglobulin G -- IL Interleukin -- MEM Minimum essential medium -- MHC Major histocompatibility complex -- PMA Phorbol 12-myristate-13-acetate -- PMSF Phenylmethylsulfonyl fluoride -- Th T helper cell -- TMB 3, 3′, 5, 5′ tetramethylbenzidine -- V-DC Dendritic cells transfected with vector plasmid DNA; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.01.034
• Languages: English
• ISSNs: 0264-410X

Abstract

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.