TY - JOUR
T1 - Vaccine-mediated immune responses to experimental pulmonary cryptococcus gattii infection in mice
AU - Chaturvedi, Ashok K.
AU - Hameed, Rumanasma S.
AU - Wozniak, Karen L.
AU - Hole, Camaron R.
AU - Wager, Chrissy M.Leopold
AU - Weintraub, Susan T.
AU - Lopez-Ribot, Jose L.
AU - Wormley, Floyd L.
PY - 2014/8/13
Y1 - 2014/8/13
N2 - Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.
AB - Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.
UR - https://www.scopus.com/pages/publications/84905911983
UR - https://www.scopus.com/pages/publications/84905911983#tab=citedBy
U2 - 10.1371/journal.pone.0104316
DO - 10.1371/journal.pone.0104316
M3 - Article
C2 - 25119981
AN - SCOPUS:84905911983
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 8
M1 - e104316
ER -