Glucan-chitin particles enhance Th17 response and improve protective efficacy of a multivalent antigen (rCpa1) against pulmonary Coccidioides posadasii infection

Chiung Yu Hung, Hao Zhang, Natalia Castro-Lopez, Gary R. Ostroff, Payam Khoshlenar, Ambily Abraham, Garry T. Cole, Austin Negron, Thomas Forsthuber, Tao Peng, John N. Galgiani, Neil M. Ampel, Jieh Juen Yu

Research output: Contribution to journalArticle

10 Scopus citations

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 -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 -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.

Original languageEnglish (US)
Article numbere00070-18
JournalInfection and Immunity
Volume86
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Adaptive immunity
  • Coccidioides
  • Coccidioidomycosis
  • Fungal vaccine
  • HLA-DR transgenic mice
  • Th17
  • Th17 response
  • Vaccine immunity

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Hung, C. Y., Zhang, H., Castro-Lopez, N., Ostroff, G. R., Khoshlenar, P., Abraham, A., Cole, G. T., Negron, A., Forsthuber, T., Peng, T., Galgiani, J. N., Ampel, N. M., & 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), [e00070-18]. https://doi.org/10.1128/IAI.00070-18