Passive antibody therapy for infectious diseases

Casadevall, Arturo; Dadachova, Ekaterina; Pirofski, Liise Anne

doi:10.1038/nrmicro974

Cited by 481 publications

(403 citation statements)

References 60 publications

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“…Antibodies are natural products of the immune system and interact with other immune components. Protective mAb may act through complement-mediated lysis, enhancement, or inhibition of phagocytosis, Fc-mediated cytokine release, and direct antimicrobial effects [19]. Our results showed that yeast cells opsonized with anti-70-kDa protein mAb had increased the phagocytic index.…”

Section: Discussionmentioning

confidence: 63%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that specific antibodies show different degrees of protection against mycosis. In a previous study, antigens secreted by Sporothrix schenckii induced a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of antibodies to this antigen in infection control. In the present study, an IgG1 mAb was produced against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell-deficient mice were used. Moreover, in a second schedule treatment, the mAb was injected after infection was established, and again we observed a significant reduction in CFU associated with an increase of IFN-cproduction. Also, the 70-kDa antigen is shown to be a putative adhesin present on the surface of this fungus. In conclusion, we report for the first time the protective effect of a specific antibody against S. schenckii.Key words: Adhesins . Mab . Passive immunization . Sporothrix schenckii . Sporotrichosis IntroductionSporotrichosis is a chronic subcutaneous mycosis that occurs worldwide. However, this disease is commonly seen in tropical and subtropical regions [1]. It is caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii, which is an ubiquitous environmental saprophyte that can be isolated from soil and plant debris [2]. In the past, infections were limited to the cutaneous forms of the disease.Recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromised individuals [3,4].The immunological mechanisms involved in prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting The host against S. schenckii [5]. In experimental infections, athymic nude mice are more susceptible to sporotrichosis, and acquired immunity against S. schenckii is mainly mediated by T-cell-activated macrophages [6,7].In contrast, the role of the humoral immune response in protection against this fungus has not been studied in detail. In a previous study, we showed that antigens secreted by S. 3080induce a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of specific antibodies to this molecule in infection control [8].Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that antibodies with defined specificity show different degrees of protection against mycosis [9]. Administration of mAb-mediated protection against Paracoccidioides brasiliensis and Candida albicans and modif...

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Section: Discussionmentioning

confidence: 63%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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“…First, the corresponding mRNAs are matured and translated in the rough ER; then their nascent polypeptides are translocated into the ER and the N-terminal signal peptide is subsequently cleaved; folding is assisted by ER resident chaperones as the Immunoglobulin Heavy Chain Binding Protein (BiP) [37]. Besides, the Endoplasmic Reticulum Associated Protein Degradation (ERAD) quality control mechanism ensures that unfolded antibody chains are removed from the ER and degraded via the proteosome [38]. Finally, antibody chains are linked together by disulfide bonds established by ER-resident protein disulfide isomerase (PDI) [39].…”

Section: Deleted: Alsomentioning

confidence: 99%

“…Besides, the Endoplasmic Reticulum Associated Protein Degradation (ERAD) quality control mechanism ensures that unfolded antibody chains are removed from the ER and degraded via the proteosome [38]. Finally, antibody chains are linked together by disulfide bonds established by ER-resident protein disulfide isomerase (PDI) [39].…”

Section: Acknowledgementsmentioning

confidence: 99%

Manufacturing antibodies in the plant cell

Orzáez

Granell

Blázquez

2009

Biotechnology Journal

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International audiencePlants have long been considered advantageous platforms for large-scale production of antibodies due to their low cost, scalability, and the low chances of pathogen contamination. Much effort has therefore been devoted to efficiently produce mAbs (from nanobodies to secretory antibodies) in plant cells. Several technical difficulties have been encountered and are being coped with. Improvements in production levels have been achieved by manipulation of gene expression and, more efficiently, of cell targeting and protein folding and assembly. Differences in mAb glycosylation patterns between animal and plant cells are being successfully addressed by the elimination and introduction of the appropriate enzyme activities in plant cells. Another relevant battlefield is the dichotomy between production capacity and speed. Classically, stably transformed plant lines have been proposed for large scale mAb production, whereas the use of transient expression systems has always provided production speed at the cost of scalability. However, recent advances in transient expression techniques have brought impressive yield improvements, turning speed and scalability highly compatible assets. In the era of personalized medicines, the combination of yield and speed, and the advances in glyco-engineering have made the plant cell a serious contender in the field of recombinant antibody production

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“…This technology allowed the production of large quantities of homogeneous antibodies of a single isotype in tissue culture and monoclonal antibodies became powerful agents in the treatment and diagnosis of diseases, as well as important research tools (Casadevall et al, 2004;Stacy, 2005). Since its inception, the major drawback of the hybridoma technology has been that it recovers only a tiny percent of the B cells that are making antibody to a particular antigen at the time of fusion.…”

Section: Introductionmentioning

confidence: 99%

Forced expression of AID facilitates the isolation of class switch variants from hybridoma cells

Iglesias-Ussel

Fan

et al. 2006

Journal of Immunological Methods

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Monoclonal antibodies are used in the treatment and diagnosis of diseases and to study the protective and adverse functions of antibodies in vitro and in vivo. Since the isotype determines the effector function, half-life in the serum and distribution throughout the body, it would be useful to have a battery of antibodies with the same binding site associated with different isotypes. However, since hybridomas switch isotypes at very low frequencies in tissue culture, it has been difficult and very labor intensive to isolate panels of class switch variants. We show here that stable transfection of activation-induced cytidine deaminase (AID) in hybridomas increased their frequency of switching to a level that greatly facilitated the isolation of subclones expressing monoclonal antibodies of different isotypes. Although forced expression of AID also increased the frequency of somatic hypermutation in the immunoglobulin variable regions that encode the antigen-binding site, antigen recognition was retained in the isotype switched antibodies.

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Passive antibody therapy for infectious diseases

Cited by 481 publications

References 60 publications

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Manufacturing antibodies in the plant cell

Forced expression of AID facilitates the isolation of class switch variants from hybridoma cells

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