Complement and Fc Function Are Required for Optimal Antibody Prophylaxis against<i>Pneumocystis carinii</i>Pneumonia

Wells, Jesse; Haidaris, Constantine G.; Wright, Terry W.; Gigliotti, Francis

doi:10.1128/iai.74.1.390-393.2006

Cited by 26 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years additional mechanisms of antibody action against fungi have been revealed, including growth inhibition (42), inhibition of biofilm formation (22), inhibition of adherence (24), inhibition of germination (24), and direct antifungal effects (24). For antibodies to C. albicans mannoproteins, Pneumocystis carinii surface antigen, and C. neoformans glucuronoxylomannan, the Fc region and/or complement was essential for antibody efficacy (15,41,44), whereas the activity of antibodies to other C. albicans mannoproteins (MP65) and heat shock protein 90 (9, 29) is mediated by antibody fragments (Fabs) and does not require Fc regions. Notably, antibodies to C. albicans MP65 and secretory aspartyl proteinase-2 that lack Fc regions were shown to inhibit fungal adherence to epithelial cells (9).…”

Section: Mechanisms Of Antibody-mediated Protectionmentioning

confidence: 99%

Antibody-Mediated Protection through Cross-Reactivity Introduces a Fungal Heresy into Immunological Dogma

Casadevall

Pirofski

2007

Infect Immun

View full text Add to dashboard Cite

Section: Mechanisms Of Antibody-mediated Protectionmentioning

confidence: 99%

Antibody-Mediated Protection through Cross-Reactivity Introduces a Fungal Heresy into Immunological Dogma

Casadevall

Pirofski

2007

Infect Immun

View full text Add to dashboard Cite

“…We have previously shown that administration of a Pca1-binding MAb (4F11) reduces organism burden, and maximal reduction of Pneumocystis after MAb infusion requires an intact Fc region and a functional complement system (29). Persistence of protection well after immunization and in the absence of CD4 ϩ T cells also is most consistent with antibody-mediated protection.…”

Section: Discussionmentioning

confidence: 71%

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4 ϩ T cells were depleted, and the mice were exposed to Pneumocystis murina. Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii. Potential orthologs of Pca1 have been identified in P. jirovecii. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.

show abstract

“…Antibody responses to surface proteins have been associated with protection from Pneumocystis pneumonia using both active and passive immunization approaches (1)(2)(3)(4)(5). These data suggest that antibody responses raised against surface epitopes can provide protection against Pneumocystis pneumonia potentially by enhancing opsonic phagocytosis or through activation of complement (6,7). A limitation of antigen discovery is the fact that Pneumocystis cannot be cultured in vitro.…”

mentioning

confidence: 99%

Novel Pneumocystis Antigen Discovery Using Fungal Surface Proteomics

et al. 2014

View full text Add to dashboard Cite

b Pneumonia due to the fungus Pneumocystis jirovecii is a life-threatening infection that occurs in immunocompromised patients. The inability to culture the organism as well as the lack of an annotated genome has hindered antigen discovery that could be useful in developing novel vaccine-or antibody-based therapies as well as diagnostics for this infection. Here we report a novel method of surface proteomics analysis of Pneumocystis murina that reliably detected putative surface proteins that are conserved in Pneumocystis jirovecii. This technique identified novel CD4؉ T-cell epitopes as well as a novel B-cell epitope, Meu10, which encodes a glycosylphosphatidylinositol (GPI)-anchored protein thought to be involved in ascospore assembly. The described technique should facilitate the discovery of novel target proteins for diagnostics and therapeutics for Pneumocystis infection. Pneumocystis pneumonia (PCP) is a significant cause of mortality and morbidity in immunocompromised patients. There are limited therapeutic choices other than trimethoprim-sulfamethoxazole (TMP-SMX). Antibody responses to surface proteins have been associated with protection from Pneumocystis pneumonia using both active and passive immunization approaches (1-5). These data suggest that antibody responses raised against surface epitopes can provide protection against Pneumocystis pneumonia potentially by enhancing opsonic phagocytosis or through activation of complement (6, 7). A limitation of antigen discovery is the fact that Pneumocystis cannot be cultured in vitro. A recently described tool that may facilitate antigen discovery for fungi is the use of the specific labeling of fungal cell surface proteins followed by proteomic analysis using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) for the study of both the localization and function (8) of fungal surface proteins (9). This approach allows the characterization of cell surface proteins on living cell surfaces, and we hypothesized that this technique could also be applied to noncultivatable fungi such as Pneumocystis and facilitate antigen discovery.In this study, we developed a novel surface protein-labeling protocol using Pneumocystis murina. We propagated and harvested high-yield P. murina from Rag2 Ϫ/Ϫ Il2rg Ϫ/Ϫ mice (10). The surface proteins of purified P. murina were biotin labeled and analyzed using LC-MS to determine peptide sequences and sites of N-hydroxysuccinimide (NHS) ester labeling. The tandem mass spectral data of peptides were then used to query the NCBI RefSeq protein sequence for fungi (Taxonomy identification no.[ID] 4751) and the P. murina draft genome database to identify peptides (11). We identified major surface glycoproteins (MSGs) as well as a set of novel cell surface proteins and selected 8 non-MSG protein sequences for further study. To determine if these proteins were seen by the immune system as CD4 ϩ T-cell epitopes, we analyzed these proteins for putative major histocompatibility complex class II (MHCII) binding, synthesized peptides from t...

show abstract

Complement and Fc Function Are Required for Optimal Antibody Prophylaxis againstPneumocystis cariniiPneumonia

Cited by 26 publications

References 30 publications

Antibody-Mediated Protection through Cross-Reactivity Introduces a Fungal Heresy into Immunological Dogma

Antibody-Mediated Protection through Cross-Reactivity Introduces a Fungal Heresy into Immunological Dogma

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

Novel Pneumocystis Antigen Discovery Using Fungal Surface Proteomics

Contact Info

Product

Resources

About