The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Liise Anne Pirofski - One of the best experts on this subject based on the ideXlab platform.
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The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19.
mBio, 2021Co-Authors: Arturo Casadevall, Liise Anne Pirofski, Michael J. JoynerAbstract:Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered Antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial Therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent Antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage Therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that Antibody Therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of Antibody Therapy, namely, specificity, temporal, and quantitative principles, connoting that Antibody efficacy requires the administration of specific Antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum Therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of Antibody Therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases
PLOS Pathogens, 2015Co-Authors: Arturo Casadevall, Liise Anne PirofskiAbstract:The current Ebola epidemic provides a dramatic example of the potential of passive Antibody Therapy for infectious diseases that is also instructive of the hurdles and limitations involved in wide-scale reintroduction of this powerful anti-infective strategy. Passive Antibody Therapy was first used in the 1890s as "serum Therapy" and was the first effective anti-infective Therapy. Serum Therapy was largely discontinued with the advent of antibiotic Therapy in the early 1940s because it could not compete with regards to cost or ease of administration and had additional complexities, including that it had to be administered early in disease, it manifested lot-to-lot variation, and its efficacy required immune donors and the availability of a specific microbiological diagnosis so sera could be matched to the disease-causing microorganism [1]. Serum Therapy using heterologous sera was also associated with "serum sickness," a syndrome caused by the formation of antigen-Antibody complexes. However, antibiotic Therapy was never shown to be superior in efficacy to Antibody Therapy and there were some conditions, such as pneumococcal pneumonia, where it may have had some advantages. Despite their wholesale abandonment, Antibody therapies did retain a niche for certain conditions where no drugs were available, such as the prevention and/or treatment of tetanus, botulism, and certain viral diseases. The development of hybridoma technology and monoclonal antibodies (mAbs) in the mid-1970s promised to solve many of the problems of serum Therapy, but, to date, there has not been formal reintroduction of Antibody therapies for infectious diseases despite considerable and ongoing efforts to develop such therapies against viral diseases, such as HIV infection, and bacterial diseases, such as those caused by Pseudomonas aeruginosa and Staphylacoccous aureus. In contrast, mAbs have revolutionized the treatment of many cancers and rheumatic diseases and dozens have been licensed. Here we analyze why Ab-based therapies remain so underdeveloped for infectious diseases through the prism of the Ebola epidemic.
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Passive Antibody Therapy for infectious diseases
Nature Reviews Microbiology, 2004Co-Authors: Arturo Casadevall, Ekaterina Dadachova, Liise Anne PirofskiAbstract:Passive Antibody Therapy is not a new technique. Behring and Kitasato discovered that specific antibodies could protect against bacterial toxins in the early 1890s and, by the 1930s, serum Therapy was being widely used to treat a variety of infectious diseases. However, the increase in the popularity of serum Therapy occurred at about the same time as the first antibiotics were developed, and as antibiotics became more widely available, so the use of serum Therapy declined. By the late 1940s it had largely been abandoned. In recent years there has been renewed interest in using passive Antibody Therapy to treat infectious diseases. However, at present, although immunoglobulin preparations are available to treat some infections, such as hepatitis B, rabies and varicella–zoster virus, only one monoclonal Antibody (palivizumab) has been licensed to prevent an infectious disease. The advantages of using Antibody molecules to treat infectious diseases include their specificity and versatility. Antibodies are capable of mediating a variety of different biological effects including both those that are independent of other components of the host immune system, such as neutralizing toxins and viruses and activating complement, and effects that involve other components of the host immune system, such as Antibody-dependent cellular cytotoxicity and opsonization. Additionally, the effects of antibodies can be synergistic with those of conventional antimicrobial therapies, and the time to develop therapeutic Antibody preparations would be considerably shorter than the development time for a vaccine. One of the most important advantages of using antibodies is that they can be easily modified to target host cells. One such strategy is radioimmunoTherapy, in which a radionuclide is attached to an Antibody molecule. As an intact immune system is not required, radioimmunoTherapy could be particularly effective in immunocompromised hosts. As infected cells can be killed by a 'crossfire' effect, radioimmunoTherapy might also be useful to target intracellular pathogens and chronic infections. The high specificity of antibodies can also be a disadvantage when considering Antibody-based therapies because accurate diagnosis of the causative microbial agent of an infection is necessary and a 'cocktail' of different antibodies might be required to treat infections with a microorganism that undergoes antigenic variation. As the efficacy of therapeutic Antibody preparations decreases with time, this might mean that they are best applied to infections where early diagnosis is possible. Additionally, the costs associated with Antibody treatments can be higher than treatment with conventional antimicrobial agents; however, the increased costs of the treatment should be offset against the lower rates of resistance associated with Antibody Therapy. Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many Antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that Antibody-based therapies are the only means to provide immediate immunity against biological weapons. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of Antibody-based Therapy for the prevention and treatment of infectious diseases.
Arturo Casadevall - One of the best experts on this subject based on the ideXlab platform.
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The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19.
mBio, 2021Co-Authors: Arturo Casadevall, Liise Anne Pirofski, Michael J. JoynerAbstract:Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered Antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial Therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent Antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage Therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that Antibody Therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of Antibody Therapy, namely, specificity, temporal, and quantitative principles, connoting that Antibody efficacy requires the administration of specific Antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum Therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of Antibody Therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases
PLOS Pathogens, 2015Co-Authors: Arturo Casadevall, Liise Anne PirofskiAbstract:The current Ebola epidemic provides a dramatic example of the potential of passive Antibody Therapy for infectious diseases that is also instructive of the hurdles and limitations involved in wide-scale reintroduction of this powerful anti-infective strategy. Passive Antibody Therapy was first used in the 1890s as "serum Therapy" and was the first effective anti-infective Therapy. Serum Therapy was largely discontinued with the advent of antibiotic Therapy in the early 1940s because it could not compete with regards to cost or ease of administration and had additional complexities, including that it had to be administered early in disease, it manifested lot-to-lot variation, and its efficacy required immune donors and the availability of a specific microbiological diagnosis so sera could be matched to the disease-causing microorganism [1]. Serum Therapy using heterologous sera was also associated with "serum sickness," a syndrome caused by the formation of antigen-Antibody complexes. However, antibiotic Therapy was never shown to be superior in efficacy to Antibody Therapy and there were some conditions, such as pneumococcal pneumonia, where it may have had some advantages. Despite their wholesale abandonment, Antibody therapies did retain a niche for certain conditions where no drugs were available, such as the prevention and/or treatment of tetanus, botulism, and certain viral diseases. The development of hybridoma technology and monoclonal antibodies (mAbs) in the mid-1970s promised to solve many of the problems of serum Therapy, but, to date, there has not been formal reintroduction of Antibody therapies for infectious diseases despite considerable and ongoing efforts to develop such therapies against viral diseases, such as HIV infection, and bacterial diseases, such as those caused by Pseudomonas aeruginosa and Staphylacoccous aureus. In contrast, mAbs have revolutionized the treatment of many cancers and rheumatic diseases and dozens have been licensed. Here we analyze why Ab-based therapies remain so underdeveloped for infectious diseases through the prism of the Ebola epidemic.
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Passive Antibody Therapy for infectious diseases
Nature Reviews Microbiology, 2004Co-Authors: Arturo Casadevall, Ekaterina Dadachova, Liise Anne PirofskiAbstract:Passive Antibody Therapy is not a new technique. Behring and Kitasato discovered that specific antibodies could protect against bacterial toxins in the early 1890s and, by the 1930s, serum Therapy was being widely used to treat a variety of infectious diseases. However, the increase in the popularity of serum Therapy occurred at about the same time as the first antibiotics were developed, and as antibiotics became more widely available, so the use of serum Therapy declined. By the late 1940s it had largely been abandoned. In recent years there has been renewed interest in using passive Antibody Therapy to treat infectious diseases. However, at present, although immunoglobulin preparations are available to treat some infections, such as hepatitis B, rabies and varicella–zoster virus, only one monoclonal Antibody (palivizumab) has been licensed to prevent an infectious disease. The advantages of using Antibody molecules to treat infectious diseases include their specificity and versatility. Antibodies are capable of mediating a variety of different biological effects including both those that are independent of other components of the host immune system, such as neutralizing toxins and viruses and activating complement, and effects that involve other components of the host immune system, such as Antibody-dependent cellular cytotoxicity and opsonization. Additionally, the effects of antibodies can be synergistic with those of conventional antimicrobial therapies, and the time to develop therapeutic Antibody preparations would be considerably shorter than the development time for a vaccine. One of the most important advantages of using antibodies is that they can be easily modified to target host cells. One such strategy is radioimmunoTherapy, in which a radionuclide is attached to an Antibody molecule. As an intact immune system is not required, radioimmunoTherapy could be particularly effective in immunocompromised hosts. As infected cells can be killed by a 'crossfire' effect, radioimmunoTherapy might also be useful to target intracellular pathogens and chronic infections. The high specificity of antibodies can also be a disadvantage when considering Antibody-based therapies because accurate diagnosis of the causative microbial agent of an infection is necessary and a 'cocktail' of different antibodies might be required to treat infections with a microorganism that undergoes antigenic variation. As the efficacy of therapeutic Antibody preparations decreases with time, this might mean that they are best applied to infections where early diagnosis is possible. Additionally, the costs associated with Antibody treatments can be higher than treatment with conventional antimicrobial agents; however, the increased costs of the treatment should be offset against the lower rates of resistance associated with Antibody Therapy. Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many Antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that Antibody-based therapies are the only means to provide immediate immunity against biological weapons. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of Antibody-based Therapy for the prevention and treatment of infectious diseases.
Gary P. Kobinger - One of the best experts on this subject based on the ideXlab platform.
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Antibody Therapy for Ebola: Is the tide turning around?
Human vaccines & immunotherapeutics, 2014Co-Authors: Xiangguo Qiu, Gary P. KobingerAbstract:Ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and CDC Category A Agents of Bioterrorism. To date, there are no approved therapies and vaccines available to treat these infections. Antibody Therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely combat infectious diseases. Passive immunization for Ebola virus was successful in 2012, after over 15 years of failed attempts leading to skepticism that the approach would ever be of potential benefit. Currently, monoclonal Antibody (mAbs)-based therapies are the most efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates, which recapitulate the human disease with the highest similarity. Novel combinations of mAbs can even fully cure lethally infected animals after clinical sy...
Xiangguo Qiu - One of the best experts on this subject based on the ideXlab platform.
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Antibody Therapy for Ebola: Is the tide turning around?
Human vaccines & immunotherapeutics, 2014Co-Authors: Xiangguo Qiu, Gary P. KobingerAbstract:Ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and CDC Category A Agents of Bioterrorism. To date, there are no approved therapies and vaccines available to treat these infections. Antibody Therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely combat infectious diseases. Passive immunization for Ebola virus was successful in 2012, after over 15 years of failed attempts leading to skepticism that the approach would ever be of potential benefit. Currently, monoclonal Antibody (mAbs)-based therapies are the most efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates, which recapitulate the human disease with the highest similarity. Novel combinations of mAbs can even fully cure lethally infected animals after clinical sy...
C. M. Lockwood - One of the best experts on this subject based on the ideXlab platform.
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long term remission of intractable systemic vasculitis with monoclonal Antibody Therapy
The Lancet, 1993Co-Authors: C. M. Lockwood, S Thiru, John D Isaacs, G Hale, Herman WaldmannAbstract:Monoclonal antibodies that target T cells offer an alternative to conventional immunosuppressive drugs in the management of autoimmune disease. "Humanisation" of such monoclonal antibodies makes their clinical use less likely to be prone to the risk of cross-species sensitisation than treatment with rodent antibodies. We describe humanised monoclonal Antibody Therapy in four patients with severe systemic vasculitis unresponsive to immunosuppressive drugs. Substantial and sustained benefit was seen in three of the four patients, although one of these three patients developed anti-idiotypic antibodies that had to be removed by plasma exchange.
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Monoclonal Antibody Therapy for vasculitis.
Advances in experimental medicine and biology, 1993Co-Authors: C. M. LockwoodAbstract:This presentation discusses the use of “humanised” monoclonal anti T cell Antibody Therapy for the treatment of patients with refractory systemic vasculitis.