An alternative for human antibody generation is the use of transgenic animals in which the animal antibody gene repertoire is substituted with the corresponding human gene repertoire, but also this technology is limited by the restrictions of the immune system. The human hybridoma technology allows the generation of human antibodies, ( Cole etВ al., 1984 Hammond, 2010), but this approach will not be able to deliver antibodies against any targets because specific B-cells from humans would be needed and this is limited by ethical constraints. While various humanization strategies are available to reduce the immunogenicity, these approaches are often laborious ( Almagro and Fransson, 2008 Lo K.-M. But, the therapeutic applications of murine antibodies are very limited because repeated administration of murine antibodies can cause a human anti-mouse antibody reaction (HAMA), which can lead also to severe side effects such as anaphylactic shock ( Courtenay-Luck etВ al., 1986). The hybridoma technology most commonly provides murine antibodies for use in research and diagnostics. Other limitations of the hybridoma technology are the possible instability of the tetraploid, but also often aneuploid hybridoma cell lines ( Pauza etВ al., 1993), the restriction of the immune system which prevents the generation of antibodies against highly conserved or self-antigens and most important the limitations to directly generate human antibodies ( Winter and Milstein, 1991). Of 185 randomly selected hybridomas analyzed in this study, almost one third was found to contain additional productive heavy or light chains, resulting in antibodies with reduced affinity and more than one specificity. Despite these antibodies are monoclonal, cell secreted antibodies are not always monospecific, as unveiled by the results of a multicentric study on the detrimental effects of genetic diversity in individual hybridoma clones ( Bradbury etВ al., 2018). The hybridoma technology was a milestone in antibody generation because it allowed the production of monoclonal antibodies ( KГ¶hler and Milstein, 1975). In the past - and still todayВ - polyclonal antibodies (blood serum) are produced in animals like horses ( von Behring and Kitasato, 1890). 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.ДЄntibodies are indispensable tools for basic research ( Colwill and GrГ¤slund, 2011), diagnostics ( Kourea and Kotoula, 2016) and therapy ( Kaplon and Reichert, 2021). Therefore, the selected antibody fragments can be rapidly further engineered in any needed antibody format according to the requirements of the final application. A further advantage is the availability of the DNA sequence encoding the phage displayed antibody fragment, which is packaged in the phage particles.

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

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