{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:14:08Z","timestamp":1770333248841,"version":"3.49.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The vaccine efficacy of the gene sequence encoding the signal peptide of the antigen known as antigen 2 or proline-rich antigen (Ag2\/PRA), an immunodominant antigen present in the cell wall of the fungal pathogen<jats:italic>Coccidioides immitis<\/jats:italic>, was investigated in a murine model of coccidioidomycosis. Expression plasmids for Ag2\/PRA(1-18) DNA (signal sequence), Ag2\/PRA(19-194) DNA (lacking the signal sequence), and Ag2\/PRA(1-194) DNA (full length) were inserted in the pVR1012 vector, and the constructs were used to vaccinate the highly susceptible BALB\/c mouse strain. Immunization with the signal gene sequence significantly reduced the fungal burden in the lungs and spleens of mice 12 days after intraperitoneal challenge with a lethal dose of 2,500<jats:italic>C. immitis<\/jats:italic>arthroconidia, to a level comparable to the protection induced in mice immunized with the full-length Ag2\/PRA(1-194) DNA. The Ag2\/PRA(19-194) gene protected mice but to a significantly lower level than the signal sequence or the full-length Ag2 gene. The immunizing capacity of Ag2\/PRA(1-18) was not attributable to a nonspecific immunostimulatory effect of DNA, as evidenced by the fact that mice immunized with a frameshift mutation of Ag2\/PRA(1-18) were not protected against challenge. Furthermore, a synthetic peptide corresponding to the translated sequence of Ag2\/PRA(1-18) DNA protected mice, albeit at a lower level than the Ag2\/PRA(1-18) DNA vaccine. The protection induced with the signal gene vaccine correlated with the production of gamma interferon when splenocytes from Ag2\/PRA(1-18)-immunized mice were stimulated with recombinant full-length Ag2 and was not associated with the production of anti-<jats:italic>Coccidioides<\/jats:italic>immunoglobulin G antibody. This is the first study to establish that a signal peptide sequence alone, administered as a gene vaccine or synthetic peptide, can induce protective immunity against a microbial pathogen.<\/jats:p>","DOI":"10.1128\/iai.70.7.3539-3545.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:14Z","timestamp":1027764554000},"page":"3539-3545","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Role of Signal Sequence in Vaccine-Induced Protection against Experimental Coccidioidomycosis"],"prefix":"10.1128","volume":"70","author":[{"given":"Chengyong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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Douglas","family":"Ivey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca A.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.2935-2940.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/165.4.710"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1054\/tuld.1998.0196"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.2.440"},{"key":"e_1_3_2_6_2","unstructured":"Cox R. A. 1989. Antigenic structure of Coccidioides immitis p. 133-170. In E. Kurstak G. 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