Multivalent recombinant protein vaccine against coccidioidomycosis.
Coccidioidomycosis is a human respiratory disease that is endemic to the southwestern United States and is caused by inhalation of the spores of a desert soilborne fungus. Efforts to develop a vaccine against this disease have focused on identification of T-cell-reactive antigens derived from the parasitic cell wall which can stimulate protective immunity against Coccidioides posadasii infection in mice. We previously described a productive immunoproteomic/bioinformatic approach to the discovery of vaccine candidates which makes use of the translated genome of C. posadasii and a computer-based method of scanning deduced sequences of seroreactive proteins for epitopes that are predicted to bind to human major histocompatibility (MHC) class II-restricted molecules. In this study we identified a set of putative cell wall proteins predicted to contain multiple, promiscuous MHC II binding epitopes. Three of these were expressed by Escherichia coli, combined in a vaccine, and tested for protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived beyond 90 days after intranasal challenge, and the majority cleared the pathogen. We suggest that the multicomponent vaccine stimulates a broader range of T-cell clones than the single recombinant protein vaccines and thereby may be capable of inducing protection in an immunologically heterogeneous human population.
Tarcha
Eric J
EJ
Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, Ohio 43614, USA.
Basrur
Venkatesha
V
Hung
Chiung-Yu
CY
Gardner
Malcolm J
MJ
Cole
Garry T
GT
D000595:Amino Acid Sequence; D000818:Animals; D002473:Cell Wall / Q000737:chemistry; D003045:Coccidioides / Q000737:chemistry / Q000276:immunology*; D003047:Coccidioidomycosis / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics / Q000627:therapeutic use*; D005657:Fungal Vaccines / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D040901:Proteomics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D018984:Epitopes, T-Lymphocyte; D005656:Fungal Proteins; D005657:Fungal Vaccines; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic