Maize-Produced Ag2 as a Subunit Vaccine for Valley Fever
Hayden, Celine A. ; Hung, Chiung-Yu ; Zhang, Hao ; Negron, Austin ; Esquerra, Raymond ; Ostroff, Gary R ; Abraham, Ambily ; Lopez, Alejandro Gabriel ; Gonzales, Juliet Elizabeth ; Howard, John A.
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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.
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J Infect Dis. 2019 Apr 23. pii: jiz196. doi: 10.1093/infdis/jiz196. [Epub ahead of print] Link to article on publisher's site