The Friend of Man a Friend Again?: Saccharomyces (S) as a Vaccine against Invasive Aspergillosis.

J. CAPILLA1,2,3, K. V. CLEMONS 1,2,3, D. A. STEVENS 1,2,3;

Author address: 

1California Inst. for Med. Res., San Jose, CA, 2Santa Clara Valley Med. Ctr., San Jose, CA, 3Stanford Univ., Stanford, CA.

Abstract: 

Background: Aspergillus is a lethal opportunist in immunocompromised patients. We previously reported, from murine studies with S with a vector expressing Aspergillus antigens as a vaccine, that killed S with empty vector also showed protection against systemic aspergillosis, and subsequent studies with a 2nd S strain, without vector, at 107.8 heat-killed (HK) S subcutaneously (sc) day (d) 28, 21, 14 before challenge, reduced infection in the target organs, kidney and brain, p=0.05, 0.02, respectively. Methods: Male 5-wk. CD-1 mice were given the preceding regimen (reg.) HK S, (reg. A) or 107.8 live S sc, or 107.8 HK S d 35, 28, 21; d 42, 35, 28, 21; or 108.8 d 28, 21, 14, before challenge with 106.8 viable A. fumigatus conidia IV. Variations on reg. A included extra groups with adjuvants CpG or MPL. All statistical comparisons were made vs. controls. Results: Survival in all 5 basic vaccine groups above was prolonged (p=0.015-0.001). This was not improved by adjuvants. Infection in kidneys was reduced p=0.05 by reg. A and p=0.035-0.004 by the other 4 reg., and A + CpG or MPL was p=0.015, 0.003. Similarly, infection in brain was reduced p=0.09 by reg. A, A + CpG or MPL p=0.02, 0.01, and the other 4 reg. p=0.035-0.004. In another study, reg. A or increasing the HK doses to 109 affirmed survival prolongation (both p=0.004), as did use of a 3rd S strain (p=0.03); other variations in timing or number of injections also significant. Conclusions: We show sc vaccination with killed or live S is protective against lethal invasive aspergillosis, and adjuvants may enhance reduction of infection. Variations in dose and timing may improve efficacy vs. controls. S vaccination is a possible avenue to a vaccine vs. aspergillosis in the immunocompromised patient.
2007

abstract No: 

G-1708

Full conference title: 

47th Interscience Conference on Antimicrobial agents and Chemotherapy
    • ICAAC 47th