Multivalent recombinant protein vaccine against coccidioidomycosis.

Abstract

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.

• Authors: Eric J Tarcha, Venkatesha Basrur, Chiung-Yu Hung, Malcolm J Gardner, Garry T Cole
• Journal: Infection and immunity (Infect Immun) Vol. 74 Issue 10 Pg. 5802-13 (Oct 2006) ISSN: 0019-9567 [Print] United States
• PMID: 16988258 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Fungal Proteins
• Fungal Vaccines
• Histocompatibility Antigens Class II
• Immunodominant Epitopes
• Recombinant Proteins
• Vaccines, Synthetic

Topics

• Amino Acid Sequence
• Animals
• Cell Wall (chemistry)
• Coccidioides (chemistry, immunology)
• Coccidioidomycosis (prevention & control)
• Epitopes, T-Lymphocyte (immunology)
• Escherichia coli (genetics)
• Fungal Proteins (analysis, genetics, therapeutic use)
• Fungal Vaccines (therapeutic use)
• Histocompatibility Antigens Class II (immunology)
• Humans
• Immunodominant Epitopes (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Proteomics
• Recombinant Proteins (biosynthesis, genetics, therapeutic use)
• T-Lymphocytes (immunology)
• Vaccines, Synthetic (therapeutic use)