TY - JOUR
T1 - Efficacy of immune sera from human immunoglobulin transgenic mice immunized with a peptide mimotope of Cryptococcus neoformans glucuronoxylomannan
AU - Maitta, Robert W.
AU - Datta, Kausik
AU - Pirofski, Liise Anne
N1 - Funding Information:
This work was supported by National Institutes of Health grants R01AI035370, R01AI045459 and R01AI044374 (LP) and an Individual National Research Service Award F31AI010129 (RWM). Parts of this work were presented at the 101st General Meeting of the American Society for Microbiology, Orlando, FL, May 2001 (session 63, Abstract E-40, p. 337) and the 102nd General Meeting of the ASM, Salt Lake City, UT, May 2002 (session 120, Abstract F-58, p. 211).
PY - 2004/9/28
Y1 - 2004/9/28
N2 - The efficacy of antibody mediated immunity against Cryptococcus neoformans has not been established experimentally for human antibodies. Our group has previously shown that immunization with a conjugate consisting of a peptide mimotope of the C. neoformans capsular polysaccharide glucuronoxylomannan (GXM), P13, and diphtheria toxoid (P13-DT) prolonged survival of transgenic mice with human immunoglobulin loci, XenoMouse® mice, which were challenged with a lethal dose of C. neoformans. In the study reported herein, we determined the efficacy of human antibodies in the sera of immunized XenoMouse® mice against C. neoformans in passive transfer experiments in naïve BALB/c mice. Survival studies were performed with sera from XenoMouse® mice expressing human IgG2/kappa (G2/k mice) or IgG4/kappa (G4/k mice) that had been immunized with P13-tetanus toxoid (TT)/Alhydrogel with or without CpG, and G2/k mice that had been immunized with P13-DT/Alhydrogel/CpG or Alhydrogel/CpG, obtained on day 7 (early sera) and days 30 or 35-59 (late sera) after primary immunization. Compared to mice receiving sera from G2/k-PBS-treated mice, the survival of naïve mice was prolonged by both early and late sera from G2/k-P13-DT/Alhydrogel/CpG-immunized mice, but only late sera from G2/k-P13-TT/Alhydrogel/CpG-immunized mice. Late, but not early sera from G2/k-Alhydrogel/CpG-immunized mice also prolonged survival. For all sera, prolongation of survival was associated with GXM-specific serum IgM. Sera from G2/k mice that received P13-TT without CpG, and all groups of G4/k mice had low to undetectable levels of antibody to GXM and were not protective. Our findings suggest that GXM-specific human IgM may be a functional mediator of protection against C. neoformans.
AB - The efficacy of antibody mediated immunity against Cryptococcus neoformans has not been established experimentally for human antibodies. Our group has previously shown that immunization with a conjugate consisting of a peptide mimotope of the C. neoformans capsular polysaccharide glucuronoxylomannan (GXM), P13, and diphtheria toxoid (P13-DT) prolonged survival of transgenic mice with human immunoglobulin loci, XenoMouse® mice, which were challenged with a lethal dose of C. neoformans. In the study reported herein, we determined the efficacy of human antibodies in the sera of immunized XenoMouse® mice against C. neoformans in passive transfer experiments in naïve BALB/c mice. Survival studies were performed with sera from XenoMouse® mice expressing human IgG2/kappa (G2/k mice) or IgG4/kappa (G4/k mice) that had been immunized with P13-tetanus toxoid (TT)/Alhydrogel with or without CpG, and G2/k mice that had been immunized with P13-DT/Alhydrogel/CpG or Alhydrogel/CpG, obtained on day 7 (early sera) and days 30 or 35-59 (late sera) after primary immunization. Compared to mice receiving sera from G2/k-PBS-treated mice, the survival of naïve mice was prolonged by both early and late sera from G2/k-P13-DT/Alhydrogel/CpG-immunized mice, but only late sera from G2/k-P13-TT/Alhydrogel/CpG-immunized mice. Late, but not early sera from G2/k-Alhydrogel/CpG-immunized mice also prolonged survival. For all sera, prolongation of survival was associated with GXM-specific serum IgM. Sera from G2/k mice that received P13-TT without CpG, and all groups of G4/k mice had low to undetectable levels of antibody to GXM and were not protective. Our findings suggest that GXM-specific human IgM may be a functional mediator of protection against C. neoformans.
KW - Antibody-mediated immunity
KW - Cryptococcus neoformans
KW - Mimotope vaccine
UR - http://www.scopus.com/inward/record.url?scp=4444276295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4444276295&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2004.03.060
DO - 10.1016/j.vaccine.2004.03.060
M3 - Article
C2 - 15364457
AN - SCOPUS:4444276295
SN - 0264-410X
VL - 22
SP - 4062
EP - 4068
JO - Vaccine
JF - Vaccine
IS - 29-30
ER -