Dataset Information

Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.

ABSTRACT: Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal antibodies could be generated by hybridoma technology since the 70ies of the former century, nowadays antibody phage display, among other display technologies, is robustly established to discover new human monoclonal antibodies. Phage display is an in vitro technology which confers the potential for generating antibodies from universal libraries against any conceivable molecule of sufficient size and omits the limitations of the immune systems. If convalescent patients or immunized/infected animals are available, it is possible to construct immune phage display libraries to select in vivo affinity-matured antibodies. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles. Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. In this review, we present an overview of phage display derived recombinant antibodies against bacterial, viral and eukaryotic pathogens, as well as microbial toxins, intended for diagnostic and therapeutic applications.

SUBMITTER: Roth KDR

PROVIDER: S-EPMC8294040 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.

Roth Kristian Daniel Ralph KDR Wenzel Esther Veronika EV Ruschig Maximilian M Steinke Stephan S Langreder Nora N Heine Philip Alexander PA Schneider Kai-Thomas KT Ballmann Rico R Fühner Viola V Kuhn Philipp P Schirrmann Thomas T Frenzel André A Dübel Stefan S Schubert Maren M Moreira Gustavo Marçal Schmidt Garcia GMSG Bertoglio Federico F Russo Giulio G Hust Michael M

Frontiers in cellular and infection microbiology 20210707

Antibodies are essential molecules for diagnosis and treatment of diseases caused by pathogens and their toxins. Antibodies were integrated in our medical repertoire against infectious diseases more than hundred years ago by using animal sera to treat tetanus and diphtheria. In these days, most developed therapeutic antibodies target cancer or autoimmune diseases. The COVID-19 pandemic was a reminder about the importance of antibodies for therapy against infectious diseases. While monoclonal ant ...[more]

PMID: 34307196

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Project description:BackgroundEnvironmentally growing pathogens present an increasing threat for human health, wildlife and food production. Treating the hosts with antibiotics or parasitic bacteriophages fail to eliminate diseases that grow also in the outside-host environment. However, bacteriophages could be utilized to suppress the pathogen population sizes in the outside-host environment in order to prevent disease outbreaks. Here, we introduce a novel epidemiological model to assess how the phage infections of the bacterial pathogens affect epidemiological dynamics of the environmentally growing pathogens. We assess whether the phage therapy in the outside-host environment could be utilized as a biological control method against these diseases. We also consider how phage-resistant competitors affect the outcome, a common problem in phage therapy. The models give predictions for the scenarios where the outside-host phage therapy will work and where it will fail to control the disease. Parameterization of the model is based on the fish columnaris disease that causes significant economic losses to aquaculture worldwide. However, the model is also suitable for other environmentally growing bacterial diseases.ResultsTransmission rates of the phage determine the success of infectious disease control, with high-transmission phage enabling the recovery of the host population that would in the absence of the phage go asymptotically extinct due to the disease. In the presence of outside-host bacterial competition between the pathogen and phage-resistant strain, the trade-off between the pathogen infectivity and the phage resistance determines phage therapy outcome from stable coexistence to local host extinction.ConclusionsWe propose that the success of phage therapy strongly depends on the underlying biology, such as the strength of trade-off between the pathogen infectivity and the phage-resistance, as well as on the rate that the phages infect the bacteria. Our results indicate that phage therapy can fail if there are phage-resistant bacteria and the trade-off between pathogen infectivity and phage resistance does not completely inhibit the pathogen infectivity. Also, the rate that the phages infect the bacteria should be sufficiently high for phage-therapy to succeed.

Dataset Information

Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.

Publications

Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.

Similar Datasets

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