Maize-Produced Ag2 as a Subunit Vaccine for Valley Fever

J Infect Dis. 2019 Jul 19;220(4):615-623. doi: 10.1093/infdis/jiz196.

Abstract

Coccidioides is the causative agent of San Joaquin Valley fever, a fungal disease prevalent in the semiarid regions of the Americas. Efforts to develop a fungal vaccine over the last 2 decades were unsuccessful. A candidate antigen, Antigen 2 (Ag2), is notoriously difficult to express in Escherichia coli, and this study sought to accumulate the antigen at high levels in maize. Transformed maize lines accumulated recombinant Ag2 at levels >1 g/kg. Mice immunized with this antigen and challenged with live Coccidioides arthroconidia showed a reduction in the fungal load when Ag2 derived from either E. coli or maize was loaded into glucan chitin particles. A fusion of Ag2 to dendritic cell carrier peptide (DCpep) induced a T-helper type 17 response in the spleen when orally delivered, indicative of a protective immune response. The maize production platform and the glucan chitin particle adjuvant system show promise for development of a Coccidioides vaccine, but further testing is needed to fully assess the optimal method of administration.

Keywords: Coccidioides; Valley fever; bioencapsulation; glucan chitin particles; maize-produced vaccine; plant vaccine; subunit vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigens, Fungal / immunology*
  • Chitin / genetics
  • Chitin / immunology
  • Coccidioides / genetics
  • Coccidioides / immunology*
  • Coccidioidomycosis / microbiology
  • Coccidioidomycosis / prevention & control*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / immunology
  • Fungal Vaccines / immunology*
  • Glucans / genetics
  • Glucans / immunology*
  • Immunization
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins
  • Vaccines, Subunit
  • Zea mays / genetics
  • Zea mays / metabolism*

Substances

  • Adjuvants, Immunologic
  • Antigens, Fungal
  • Fungal Proteins
  • Fungal Vaccines
  • Glucans
  • Recombinant Proteins
  • Vaccines, Subunit
  • Chitin