Glucan-Chitin Particles Enhance Th17 Response and Improve Protective Efficacy of a Multivalent Antigen (rCpa1) against Pulmonary Coccidioides posadasii Infection

Date
2018-10-25
Authors
Hung, Chiung-Yu
Zhang, Hao
Castro-Lopez, Natalia
Ostroff, Gary R.
Khoshlenar, Payam
Abraham, Ambily
Cole, Garry T.
Negron, Austin
Forsthuber, Thomas
Peng, Tao
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract

Developing an effective and safe recombinant vaccine requires microbe-specific antigens combined with an adjuvant/delivery system to strengthen protective immunity. In this study, we designed and expressed a multivalent recombinant Coccidioides polypeptide antigen (rCpa1) that consists of three previously identified antigens (i.e., Ag2/Pra, Cs-Ag, and Pmp1) and five pathogen-derived peptides with high affinity for human major histocompatibility complex class II (MHC-II) molecules. The purified rCpa1 was encapsulated into four types of yeast cell wall particles containing β-glucan, mannan, and chitin in various proportions or was mixed with an oligonucleotide (ODN) containing two methylated dinucleotide CpG motifs. This multivalent antigen encapsulated into glucan-chitin particles (GCP-rCpa1) showed significantly greater reduction of fungal burden for human HLA-DR4 transgenic mice than the other adjuvant-rCpa1 formulations tested. Among the adjuvants tested, both GCPs and β-glucan particles (GPs) were capable of stimulating a mixed Th1 and Th17 response. Mice vaccinated with GCP-rCpa1 showed higher levels of interleukin 17 (IL-17) production in T-cell recall assays and earlier lung infiltration by activated Th1 and Th17 cells than GP-rCpa1-vaccinated mice. Both C57BL/6 and HLA-DR4 transgenic mice that were vaccinated with the GCP-rCpa1 vaccine showed higher survival rates than mice that received GCPs alone. Concurrently, the GCP-rCpa1 vaccine stimulated greater infiltration of the injection sites by macrophages, which engulf and process the vaccine for antigen presentation, than the GP-rCpa1 vaccine. This is the first attempt to systematically characterize the presentation of a multivalent coccidioidomycosis vaccine encapsulated with selected adjuvants that enhance the protective cellular immune response to infection.

Description
Keywords
Coccidioides, coccidioidomycosis, HLA-DR transgenic mice, fungal vaccine, vaccine immunity, Th17 response and adaptive immunity, Th17
Citation
Hung, C.-Y., Zhang, H., Castro-Lopez, N., Ostroff, G. R., Khoshlenar, P., Abraham, A., . . . Yu, J.-J. (2018). Glucan-Chitin Particles Enhance Th17 Response and Improve Protective Efficacy of a Multivalent Antigen (rCpa1) against Pulmonary Coccidioides posadasii Infection. Infection and Immunity, 86(11), 10.1128/iai.00070-00018. doi:doi:10.1128/iai.00070-18
Department
Molecular Microbiology and Immunology