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

6 Citations (Scopus)

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

Fingerprint

Coccidioides
Chitin
Glucans
Vaccines
Antigens
Lung
HLA-DR4 Antigen
Infection
Transgenic Mice
Coccidioidomycosis
Mannans
Th17 Cells
Peptides
Th1 Cells
Synthetic Vaccines
Interleukin-17
Antigen Presentation
Major Histocompatibility Complex
Cellular Immunity
Oligonucleotides

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

Cite this

Glucan-chitin particles enhance Th17 response and improve protective efficacy of a multivalent antigen (rCpa1) against pulmonary Coccidioides posadasii infection. / Hung, Chiung Yu; Zhang, Hao; Castro-Lopez, Natalia; Ostroff, Gary R.; Khoshlenar, Payam; Abraham, Ambily; Cole, Garry T.; Negron, Austin; Forsthuber, Thomas; Peng, Tao; Galgiani, John N; Ampel, Neil M.; Yu, Jieh Juen.

In: Infection and Immunity, Vol. 86, No. 11, e00070-18, 01.11.2018.

Research output: Contribution to journalArticle

Hung, CY, Zhang, H, Castro-Lopez, N, Ostroff, GR, Khoshlenar, P, Abraham, A, Cole, GT, Negron, A, Forsthuber, T, Peng, T, Galgiani, JN, Ampel, NM & Yu, JJ 2018, 'Glucan-chitin particles enhance Th17 response and improve protective efficacy of a multivalent antigen (rCpa1) against pulmonary Coccidioides posadasii infection', Infection and Immunity, vol. 86, no. 11, e00070-18. https://doi.org/10.1128/IAI.00070-18
Hung, Chiung Yu ; Zhang, Hao ; Castro-Lopez, Natalia ; Ostroff, Gary R. ; Khoshlenar, Payam ; Abraham, Ambily ; Cole, Garry T. ; Negron, Austin ; Forsthuber, Thomas ; Peng, Tao ; Galgiani, John N ; Ampel, Neil M. ; Yu, Jieh Juen. / Glucan-chitin particles enhance Th17 response and improve protective efficacy of a multivalent antigen (rCpa1) against pulmonary Coccidioides posadasii infection. In: Infection and Immunity. 2018 ; Vol. 86, No. 11.
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AU - Ostroff, Gary R.

AU - Khoshlenar, Payam

AU - Abraham, Ambily

AU - Cole, Garry T.

AU - Negron, Austin

AU - Forsthuber, Thomas

AU - Peng, Tao

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