title: Immune responses induced by heat killed Saccharomyces cerevisiae: a vaccine against fungal infection.
abstract: Heat-killed Saccharomyces cerevisiae (HKY) used as a vaccine protects mice against systemic aspergillosis and coccidioidomycosis. Little is known about the immune response induced by HKY vaccination, consequently our goal was to do an analysis of HKY-induced immune responses involved in protection. BALB/c mice were vaccinated subcutaneously 3 times with HKY, a protective reagent, and bronchoalveolar lavage fluid, spleen, lymph nodes, and serum collected 2-5 weeks later. Cultured spleen or lymph node cells were stimulated with HKY. Proliferation of HKY-stimulated spleen or lymph node cells was tested by Alamar Blue reduction and flow cytometry. Cytokines from lymphocyte supernatants and antibody to glycans in serum collected from HKY-vaccinated mice were measured by ELISA. The results show that HKY promoted spleen cell and lymph node cell proliferation from HKY-vaccinated mice but not from PBS-vaccinated control mice (all P<0.05). Cytokine measurement showed HKY significantly promoted IFNγ, IL-6 and IL-17A production by spleen cells and lymph node cells (all P<0.05 and P<0.01, respectively). Cytokine production by HKY-stimulated cells from PBS-vaccinated mice was lower than those from HKY-vaccinated (P<0.05). Cytokines in BAL from HKY-vaccinated were higher, 1.7-fold for IFNγ and 2.1-fold for TNFα, than in BAL from PBS-vaccinated. Flow cytometry of lymphocytes from HKY-vaccinated showed 52% of CD3(+) or 56% of CD8(+) cells exhibited cell division after stimulation with HKY, compared to non-stimulated controls (26 or 23%, respectively) or HKY-stimulated cells from PBS-vaccinated (31 or 34%). HKY also induced antibody against Saccharomyces glucan and mannan with titers 4- or 2-fold, respectively, above that in unvaccinated. Taken together, the results suggested that HKY vaccination induces significant and specific Th1 type cellular immune responses and antibodies to glucan and mannan.
authors.affiliation: California Institute for Medical Research, San Jose, CA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Karl V
authors.initials: KV
authors.lastname: Clemons
authors.forename: Marty
authors.initials: M
authors.lastname: Bigos
authors.forename: Izabela
authors.initials: I
authors.lastname: Medovarska
authors.forename: Elmer
authors.initials: E
authors.lastname: Brummer
authors.forename: David A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control; D003047:Coccidioidomycosis / Q000276:immunology / Q000517:prevention & control; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006358:Hot Temperature; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D005657:Fungal Vaccines; D015164:Vaccines, Inactivated