Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody

Dromer, Françoise; Charreire, Jeannine; Contrepois, A; Carbon, C; Yéni, Patrick

doi:10.1128/iai.55.3.749-752.1987

Cited by 220 publications

(80 citation statements)

References 22 publications

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“…The same antigen-based ELISA was used for all serologic studies. Polystyrene ELISA plates (Coming Glass Works, Corning, NY) were coated with 10/ig/ml ofthe GXM of serotype A C neoformans strain 371 according to a previously published protocol [14,24]. GXM-A was kindly provided by Drs J. Robbins and R. Schneerson (NIH, Bethesda, MD).…”

Section: Elisasmentioning

confidence: 99%

“…In vitro studies in murine cryptococcosis have demonstrated that murine monoclonal (m-MoAb) anti-cryptococcal polysaccharide (CPS) or GXM antibodies are opsonic and enhance phagocytosis of C. neoformans cells by macrophages [9][10][11]. Three independent groups have shown that passive administration of anti-CPS (or GXM) antibody prolongs survival or decreases the fungal burden in murine tissues [9,10,[14][15][16]. Murine anti-GXM antibodies elicited by infection and by GXM-tetanus toxoid (GXM-TT), a conjugate vaccine, enhance survival and reduce colony counts in C. /zeo/orOTan.$-infected mice [9,16].…”

Section: Introductionmentioning

confidence: 99%

“…Anti-CPS antibody-mediated protection in vivo, in vitro phagocytosis, and an improved prognosis in CM in the pre-AIDS era, all support a role for anti-CPS antibody in moderating or preventing cryptococcosis [9][10][11][12][13][14][15][16][17][18][19]. This study was undertaken to determine the prevalence of anti-GXM antibodies in HIV"^ and HIV~ individuals, and to determine if the development of CM in individuals with HIV infection can be correlated with antibody titre, isotype, or IgG subclass.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies to theCryptococcus neoformanscapsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV− individuals

DeShaw

Pirofski

1995

Clinical and Experimental Immunology

103

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SUMMARYMurine MoAbs to the Cryptococcus neoformans capsular glucuronoxylomannan (GXM) polysaccharide are protective in mice in vivo and in vitro. The prevalence of protective anti-GXM antibodies in human serum is unknown. To provide further insight into the human antibody response to C. neoformans we determined the prevalence, isotype, and IgG subclass utilization of human anti-GXM antibodies in HIV+ and HIV-sera by a sensitive antigen capture ELISA assay. One hundred and twenty-three sera from the Bronx Municipal Hospital Centre serum bank were studied retrospectively. Seventy were from HIV+ individuals, 10 with a history of cryptococcal meningitis (CM), and 53 were from HIV-individuals. Serum GXM determinations were also performed on 61 HIV+ sera. Our results demonstrated that anti-GXM IgG, IgA, and IgM are ubiquitous in both HIV+ (including those with CM), and HIV-sera. Anti-GXM IgA titres and total serum IgA concentration were elevated in HIV+ sera. Anti-GXM IgG antibodies were almost exclusively isotype-restricted to the IgG2 subclass. Our data also demonstrated elevations of antibovine serum albumin (BSA) titres in HIV+ sera. Taken together, our findings confirm hypergammaglobulinaemia and expansion of anti-protein (BSA) antibodies in HIV+ individuals and isotype restriction of human anti-carbohydrate (GXM) antibodies to the IgG2 subclass. Our report of ubiquitous anti-GXM antibodies of the IgG and IgA isotypes suggests that anti-GXM antibodies exist before HIV infection.

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Section: Elisasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibodies to theCryptococcus neoformanscapsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV− individuals

DeShaw

Pirofski

1995

Clinical and Experimental Immunology

103

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“…The ability of mAbs to protect against a lethal cryptococcal infection in mice was first demonstrated over three decades ago [93], with subsequent work demonstrating the efficacy of various mAbs that target the polysaccharide capsule, an essential virulence factor and the primary host-pathogen interface of Cryptococcus infection [94][95][96]. Among these, mAb 18B7 was evaluated in a Phase I clinical trial [50] and was found to produce a modest reduction in circulating cryptococcal antigen.…”

Section: Fungal Infectionsmentioning

confidence: 99%

Reassessing therapeutic antibodies for neglected and tropical diseases

et al. 2020

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In the past two decades there has been a significant expansion in the number of new therapeutic monoclonal antibodies (mAbs) that are approved by regulators. The discovery of these new medicines has been driven primarily by new approaches in inflammatory diseases and oncology, especially in immuno-oncology. Other recent successes have included new antibodies for use in viral diseases, including HIV. The perception of very high costs associated with mAbs has led to the assumption that they play no role in prophylaxis for diseases of poverty. However, improvements in antibody-expression yields and manufacturing processes indicate this is a cost-effective option for providing protection from many types of infection that should be revisited. Recent technology developments also indicate that several months of protection could be achieved with a single dose. Moreover, new methods in B cell sorting now enable the systematic identification of high-quality antibodies from humanized mice, or patients. This Review discusses the potential for passive immunization against schistosomiasis, fungal infections, dengue, and other neglected diseases.PLOS Neglected Tropical Diseases | https://doi.interactions have proved difficult to block. In addition, there has been great progress in the development of technology. Early generations of antibodies for human use were developed from mAbs developed in mice, antibodies that were then humanized. Recently, the technology used peptide and antibody display on phages, for which part of the 2018 Nobel Prize in Chemistry was awarded to Sir Gregory P. Winter [6]. More recently, new technologies have been developed to clone antibodies from memory B cells [7] or plasma B cells [8, 9], allowing the isolation of individual antibodies from patients with viral infections-approaches that can be applied to any infectious disease.A second reason for the popularity of antibodies in recent years is their success rate in clinical development. Once an antibody reaches testing in humans, it has a success rate of 17% to 25% for approval as a new medicine [10], compared with 5% to 10% for small molecules. This success rate is partly due to the exquisite selectivity of mAbs, enabling them to distinguish between closely related molecular targets. In the case of infectious disease, this selectivity can be absolute, since antibodies can be generated that are specific for the invading pathogen and do not cross-react with host tissues. This lack of cross-reactivity with human tissue can be confirmed by immunohistochemistry on both adult and embryonic tissues prior to the start of clinical trials. This is in stark contrast to small molecules, in which sometimes unexpected onand off-target safety signals are frequently seen in the later stages of clinical development, resulting in expensive late-stage attrition. In addition, antibodies show a relatively narrow range of variation in pharmacokinetic exposure, facilitating early estimation of the human effective dose. This is unlike true xenobiotics, whose metabolism an...

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“…The protective effect of mAbs in murine models of cryptococcal infection has mostly consisted of prolongation of survival in treated vs. untreated animals [67,69,70,75,79,[82][83][84][85]. Administration of mAbs also has been associated with a reduction of fungal burden in the lungs [70,86], brain [70,71,84], liver [71,87] and spleen [86,87] of treated mice. Prolonged survival in animals treated with mAbs was more frequently associated with downregulation [69,74,75] than with enhancement [82] of the inflammatory response.…”

Section: Preclinical Studies Involving Mabsmentioning

confidence: 99%

Immunotherapy of Cryptococcus infections

Antachopoulos

Walsh

2012

Clinical Microbiology and Infection

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Despite appropriate antifungal treatment, the management of cryptococcal disease remains challenging, especially in immunocompromised patients, such as human immunodeficiency virus-infected individuals and solid organ transplant recipients. During the past two decades, our knowledge of host immune responses against Cryptococcus spp. has been greatly advanced, and the role of immunomodulation in augmenting the response to infection has been investigated. In particular, the role of 'protective' Th1 (tumour necrosis factor-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-18) and Th17 (IL-23 and IL-17) and 'non-protective' Th2 (IL-4, IL-10, and IL-13) cytokines has been extensively studied in vitro and in animal models of cryptococcal infection. Immunomodulation with monoclonal antibodies against the capsular polysaccharide glucuronoxylomannan, glucosylceramides, melanin and β-glucan and, lately, with radioimmunotherapy has also yielded promising results in animal models. As a balance between sufficiently protective Th1 responses and excessive inflammation is important for optimal outcome, the effect of immunotherapy may range from beneficial to deleterious, depending on factors related to the host, the infecting organism, and the immunomodulatory regimen. Clinical evidence supporting immunomodulation in patients with cryptococcal infection remains too limited to allow firm recommendations. Limited human data suggest a role for IFN-γ. Identification of surrogate markers characterizing patients' immunological status could possibly suggest candidate patients for immunotherapy and the type of immunomodulation to be administered.

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Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody

Cited by 220 publications

References 22 publications

Antibodies to theCryptococcus neoformanscapsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV− individuals

Antibodies to theCryptococcus neoformanscapsular glucuronoxylomannan are ubiquitous in serum from HIV+ and HIV− individuals

Reassessing therapeutic antibodies for neglected and tropical diseases

Immunotherapy of Cryptococcus infections

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