Multivalent Recombinant Protein Vaccine against Coccidioidomycosis

• Published in: Infection and Immunity 2006-10, Vol.74 (10), p.5802-5813
• Main Authors: Tarcha, Eric J, Basrur, Venkatesha, Hung, Chiung-Yu, Gardner, Malcolm J, Cole, Garry T
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Applied microbiology; Biological and medical sciences; Cell Wall - chemistry; Coccidioides; Coccidioides - chemistry; Coccidioides - immunology; Coccidioidomycosis; Coccidioidomycosis - prevention & control; Epitopes, T-Lymphocyte - immunology; Escherichia coli; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Fungal and Parasitic Infections; Fungal Proteins - analysis; Fungal Proteins - genetics; Fungal Proteins - therapeutic use; Fungal Vaccines - therapeutic use; Histocompatibility Antigens Class II - immunology; Human mycoses; Humans; Immunodominant Epitopes - genetics; Immunodominant Epitopes - immunology; Infectious diseases; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Molecular Sequence Data; Mycoses; Proteomics; Recombinant Proteins - biosynthesis; Recombinant Proteins - genetics; Recombinant Proteins - therapeutic use; T-Lymphocytes - immunology; Tropical mycoses; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - therapeutic use
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00961-06

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.