Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae

Diago-Navarro, Elizabeth; Calatayud-Baselga, Isabel; Sun, Dong; Khairallah, Camille; Mann, Ian; Ulacia-Hernando, Amaia; Sheridan, Brian S.; Shi, Meiqing; Fries, Bettina C.

doi:10.1128/cvi.00456-16

Cited by 73 publications

(91 citation statements)

References 49 publications

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“…Thus, the effective ability of anti-CPS antibody to promote killing of ST258 might be increased in the susceptible host (e.g., an individual with comorbidities or immunosuppression). An immunotherapy approach for K. pneumoniae could be extended to target lineages other than ST258, and such work is ongoing (43,44). Moreover, recent studies indicated that antibodies specific for K. pneumoniae lipopolysaccharide work synergistically with antibiotics to improve outcomes in mouse infection models (20).…”

Section: Resultsmentioning

confidence: 99%

Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Kobayashi

Porter

Freedman

et al. 2018

mBio

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Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenic wzy deletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serum in vitro. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics.IMPORTANCE Infections caused by carbapenem-resistant K. pneumoniae are difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrugresistant bacteria. A strain of carbapenem-resistant K. pneumoniae, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistant K. pneumoniae lineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistant K. pneumoniae infections is feasible and has merit.

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Section: Resultsmentioning

confidence: 99%

Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Kobayashi

Porter

Freedman

et al. 2018

mBio

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“…Kupffer cells lining the liver sinusoids are professional resident phagocytes that first encounter gut-derived bacteria and have been described as a highly effective filtering system between the digestive system and the rest of the body (11). It has been reported that depletion of Kupffer cells significantly increased the susceptibility of host mice to Listeria monocytogenes infection, resulting in 100% mortality of mice within 3 days of infection (12).…”

mentioning

confidence: 99%

Protective Role of Kupffer Cells and Macrophages in Klebsiella pneumoniae-Induced Liver Abscess Disease

2019

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Klebsiella pneumoniae-induced liver abscess (KLA) is emerging as a leading cause of pyogenic liver abscess worldwide. In recent years, the emergence of hypervirulent K. pneumoniae (hvKp) has been strongly associated with KLA. Unlike classical K. pneumoniae, which generally infects the immunocompromised population, hvKp can cause serious and invasive infections in young and healthy individuals. hvKp isolates are often associated with the K1/K2 capsular types and possess hypermucoviscous capsules. KLA is believed to be caused by K. pneumoniae colonizing the gastrointestinal tract of the host and translocating across the intestinal barrier via the hepatic portal vein into the liver to cause liver abscess. We optimized the isolation of the liver-resident macrophages called Kupffer cells in mice and examined their importance in controlling bacterial loads during hvKp infection in healthy mice. Our study reveals the high capability of Kupffer cells to kill hvKp in vitro despite the presence of the bacterial hypermucoviscous capsule, in contrast to other macrophages, which were unable to phagocytose the bacteria efficiently. Depletion of Kupffer cells and macrophages with liposome-encapsulated clodronate (liposomal clodronate) in both an intraperitoneal and an oral mouse infection model resulted in increased bacterial loads in the livers, spleens, and lungs and increased mortality of the infected mice. Thus, Kupffer cells and macrophages are critical for the control of hvKp infection.

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“…The relevance of sex as a biological variable and rigor of experimental approaches were emphasized. Important reports on these and other trending topics were published in CVI (8)(9)(10)(11)(12)(13)(14). In this rapidly expanding scientific environment, CVI remained committed to disseminating discoveries and scientific knowledge with high scholarly and editorial standards, in line with those of other ASM journals and following the tradition and excellence of the society itself.…”

Section: A Springtime For CVImentioning

confidence: 89%

The Legacy of CVI

Pasetti

Douglas

Plaeger

2017

Clin Vaccine Immunol

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Clinical and Vaccine Immunology (CVI) will merge with the American Society for Microbiology (ASM) open-access journal mSphere in January 2018. We commemorate this transition by exploring the history of CVI and that of its predecessor, Clinical and Diagnostic Laboratory Immunology (CDLI), and by acknowledging their contributors. Research on vaccines, clinical immunology, and clinical diagnostic immunology published through mSphere will be available without restrictions to an ever-larger audience, which will expedite progress in the field. ASM remains committed to supporting its members and the research community by facilitating the dissemination of scientific knowledge in these important areas. KEYWORDS vaccines Clinical and Vaccine Immunology (CVI) begins a new phase as it merges with the American Society of Microbiology (ASM) journal mSphere in January 2018. The time is appropriate to look at the history of the journal and its contribution to the scientific community. Most importantly, it is an opportunity to acknowledge those who have accompanied us and advanced CVI's mission: authors, editors, editorial board members, reviewers, ASM staff, ASM members, and the enduringly supportive research community, to whom we are most sincerely grateful. Clinical and Diagnostic Laboratory ImmunologyThe journey started in January of 1994, when Clinical and Diagnostic Laboratory Immunology (CDLI) was launched (Fig. 1). During this time, the number of clinical immunology laboratories expanded due to the increased demand for immunologically based diagnostic tests for infectious diseases and clinical laboratory assessment of immune cell competency. Practices for standardization, quality control, and quality assurance matured simultaneously, along with the expectation of high-quality clinical laboratory standards. As the area of diagnostic laboratory immunology expanded, the Publications Board of ASM recognized the need for a journal exclusively dedicated to clinical laboratory immunology. With Dr. Steven D. Douglas as founding editor in chief (1994 to 2003), CDLI was established to facilitate dissemination of the growing body of research in the field (1). Indeed, the following decade witnessed major scientific advances in cellular immunology, molecular genetics, and immunodiagnostics. Diagnostic immunology evolved from the identification of antibodies resulting from infection to a variety of new assays using polyclonal and monoclonal antibodies to detect microbial antigens in body fluids and more-sophisticated methods for detecting antigen expression in tissue (2). Remarkable progress was also made in cellular immunology, particularly in the areas of immune deficiency, autoimmunity, inflammatory diseases, and immunopathogenesis. In vitro alternatives to skin testing for tuberculosis were developed, and flow cytometry and other methods for assessing immune function were increasingly utilized. These breakthroughs led to laboratory automation in diagnostic immunology (3). A series of commentaries by Isenberg, Rose, Fahey,...

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Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae

Cited by 73 publications

References 49 publications

Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Protective Role of Kupffer Cells and Macrophages in Klebsiella pneumoniae-Induced Liver Abscess Disease

The Legacy of CVI

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