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Infect Immun. 2018 Oct 25;86(11). pii: e00070-18. doi: 10.1128/IAI.00070-18. Print 2018 Nov.

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

Author information

1
Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas, USA Chiungyu.Hung@UTSA.edu.
2
Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas, USA.
3
Program in Molecular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
4
Valley Fever Center for Excellence, College of Medicine, University of Arizona, Tucson, Arizona, USA.
5
Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona, USA.

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.

KEYWORDS:

Coccidioides; HLA-DR transgenic mice; Th17; Th17 response and adaptive immunity; coccidioidomycosis; fungal vaccine; vaccine immunity

PMID:
30104216
PMCID:
PMC6204714
DOI:
10.1128/IAI.00070-18
[Indexed for MEDLINE]
Free PMC Article

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