Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody

R. Yuan, A. Casadevall, G. Spira, Matthew D. Scharff

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models. In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v. infection by using strains of both the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relative to controls. In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice. The results establish that isotype is important for Ab efficacy against C. neoformans.

Original languageEnglish (US)
Pages (from-to)1810-1816
Number of pages7
JournalJournal of Immunology
Volume154
Issue number4
StatePublished - 1995

Fingerprint

Immunoglobulin Class Switching
Cryptococcus neoformans
Immunoglobulin G
Antibodies
Polysaccharides
Pneumococcal Infections
Tissue Survival
Infection
Immunoglobulin A
Immunoglobulin M
Stem Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody. / Yuan, R.; Casadevall, A.; Spira, G.; Scharff, Matthew D.

In: Journal of Immunology, Vol. 154, No. 4, 1995, p. 1810-1816.

Research output: Contribution to journalArticle

@article{2d22ee81ae994b5c9100e71d80a5bec9,
title = "Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody",
abstract = "Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models. In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v. infection by using strains of both the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relative to controls. In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice. The results establish that isotype is important for Ab efficacy against C. neoformans.",
author = "R. Yuan and A. Casadevall and G. Spira and Scharff, {Matthew D.}",
year = "1995",
language = "English (US)",
volume = "154",
pages = "1810--1816",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody

AU - Yuan, R.

AU - Casadevall, A.

AU - Spira, G.

AU - Scharff, Matthew D.

PY - 1995

Y1 - 1995

N2 - Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models. In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v. infection by using strains of both the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relative to controls. In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice. The results establish that isotype is important for Ab efficacy against C. neoformans.

AB - Passively administered mAbs to Cryptococcus neoformans capsular polysaccharide can alter the course of infection in mouse models. In preliminary studies of passive Ab efficacy, most IgM, IgA, and IgG1 mAbs were protective, but the few IgG3 mAbs tested did not confer significant protection. Because IgG3 is effective in pneumococcal infections, this phenomenon was examined more rigorously by generating an IgG1 switch variant from the non-protective IgG3 mAb 3E5 and comparing its protective efficacy in a murine model of i.v. infection by using strains of both the A and D serotypes. The 3E5 IgG3 mAb did not prolong survival or reduce organ fungal burden. Rather, the IgG3 decreased survival relative to controls. In contrast, the IgG1 switch variant of 3E5 significantly prolonged survival, reduced organ colony-forming units, and reduced serum polysaccharide Ag level in infected mice. The results establish that isotype is important for Ab efficacy against C. neoformans.

UR - http://www.scopus.com/inward/record.url?scp=0028836187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028836187&partnerID=8YFLogxK

M3 - Article

C2 - 7836766

AN - SCOPUS:0028836187

VL - 154

SP - 1810

EP - 1816

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -