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Coccidioidomycosis: host response and vaccine development.
Rebecca A Cox1, D Mitchell Magee
1Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, Texas Research Park, 15355 Lambda Dr., San Antonio, TX 78245-3027, USA. coxra@uthscsa.edu.
Clinical Microbiology Reviews
|October 19, 2004
Summary
Developing a Coccidioides vaccine is feasible. While antigen 2/proline-rich antigen (Ag2/PRA) shows promise, new candidates like ELI-Ag1 and GEL-1 are needed for a more effective multivalent vaccine against coccidioidomycosis.
Area of Science:
- Mycology
- Immunology
- Vaccinology
Background:
- Coccidioidomycosis, caused by Coccidioides fungi, is a significant pathogen in the American Southwest.
- While most infections are mild, severe and lethal disease can occur, even in immunocompetent individuals.
- The feasibility of a vaccine is supported by natural immunity observed in some hosts.
Purpose of the Study:
- To evaluate existing and identify new vaccine candidates against Coccidioides.
- To improve protective efficacy beyond current subunit vaccine candidates.
- To explore the potential of multivalent vaccines for enhanced Coccidioides immunity.
Main Methods:
- Review of previous vaccine trials, including formalin-killed spherules (FKS).
- Assessment of immunodominant antigens, such as antigen 2/proline-rich antigen (Ag2/PRA).
- Genomic screening and bioinformatic approaches to identify novel protective proteins like ELI-Ag1 and GEL-1.
Main Results:
- The FKS vaccine showed limited efficacy in human trials.
- Ag2/PRA demonstrated significant protection in mouse models but was less effective than FKS and provided only partial protection upon intranasal challenge.
- New candidates, ELI-Ag1 and GEL-1, have been identified through genomic screening.
Conclusions:
- Current subunit vaccine candidates for coccidioidomycosis offer modest protection.
- A multivalent vaccine approach combining multiple antigens is hypothesized to increase protection.
- Continued research, including genomic analysis, is crucial for discovering additional candidates to achieve complete protection against pulmonary Coccidioides infection.