Proline-rich vaccine candidate antigen of Coccidioides immitis: Conservation among isolates and differential expression with spherule maturation

A proline rich antigen (PRA), which protects mice against Coccidioides immi tis, has been analyzed for differential expression and variation among isol ates. Northern blots of RNA from different stages of growth were probed wit h previously cloned cDNA and showed that mRNA for PRA increased as spherule s transformed and matured from mycelia. This pattern corresponds to the rel ative potency of whole cell vaccines from similar preparations. The PRA gen e was then cloned from a genomic library of the Silveira strain of C. immit is and its sequence analyzed. Eight other coccidioidal isolates, selected f or diversity in geographic origin and resulting clinical disease, demonstra ted heterogeneity in Southern blots and in sequences of polymerase chain re action products. Silveira differed from other California isolates at 33 of 555 bases, whereas it differed from non-California isolates by less than or equal to 2 bases. Only one of these substitutions affected protein sequenc e. Thus, tests or vaccines based on this gene are likely to cover most isol ates.