An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection

Chiung Yu Hung, Brady J. Hurtgen, Michael Bellecourt, Sam Sanderson, Edward L. Morgan, Garry T. Cole

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical vaccine exists. In this study we evaluated a novel vaccine adjuvant referred to as EP67, which is a peptide agonist of the biologically active C-terminal region of human complement component C5a. The EP67 peptide was conjugated to live spores of an attenuated vaccine strain (ΔT) of Coccidioides posadasii. The non-conjugated ΔT vaccine provided partial protection to BALB/c mice against coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67 vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67 vaccine also revealed enhanced expression of MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4 + T cells. Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides antigen-specific IgG1 and IgG2a were detected in mice immunized with the EP67-conjugated versus the non-conjugated vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to Coccidioides infection.

Original languageEnglish (US)
Pages (from-to)4681-4690
Number of pages10
JournalVaccine
Volume30
Issue number31
DOIs
StatePublished - Jun 29 2012

Fingerprint

Coccidioides
Complement C5a
agonists
Immunity
complement
Vaccines
immunity
vaccines
Infection
infection
mice
live vaccines
neutrophils
T-lymphocytes
lungs
peptides
coccidioidomycosis
vaccine adjuvants
Neutrophils
antigen-presenting cells

Keywords

  • Adjuvant
  • C5a
  • Coccidioides
  • EP67
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Hung, C. Y., Hurtgen, B. J., Bellecourt, M., Sanderson, S., Morgan, E. L., & Cole, G. T. (2012). An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. Vaccine, 30(31), 4681-4690. https://doi.org/10.1016/j.vaccine.2012.04.084

An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. / Hung, Chiung Yu; Hurtgen, Brady J.; Bellecourt, Michael; Sanderson, Sam; Morgan, Edward L.; Cole, Garry T.

In: Vaccine, Vol. 30, No. 31, 29.06.2012, p. 4681-4690.

Research output: Contribution to journalArticle

Hung, CY, Hurtgen, BJ, Bellecourt, M, Sanderson, S, Morgan, EL & Cole, GT 2012, 'An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection', Vaccine, vol. 30, no. 31, pp. 4681-4690. https://doi.org/10.1016/j.vaccine.2012.04.084
Hung CY, Hurtgen BJ, Bellecourt M, Sanderson S, Morgan EL, Cole GT. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. Vaccine. 2012 Jun 29;30(31):4681-4690. https://doi.org/10.1016/j.vaccine.2012.04.084
Hung, Chiung Yu ; Hurtgen, Brady J. ; Bellecourt, Michael ; Sanderson, Sam ; Morgan, Edward L. ; Cole, Garry T. / An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection. In: Vaccine. 2012 ; Vol. 30, No. 31. pp. 4681-4690.
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