Since heterologous animalderived antibody products are foreign proteins in humans their reactogenicity is often high. (SARSCoV2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovinederived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARSCoV2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed. Keywords:transchromosomic bovines, antibodybased therapies, bovinederived biotherapeutics, Ebola, emerging viruses, HIV1, influenza A virus, MERSCoV, SARSCoV2, Zika == 1. INTRODUCTION == Antibodies are important antiviral defenses as they have broad therapeutic potential against many infectious agents, such as Zika, Ebola, human immunodeficiency virus type 1 (HIV1), influenza A virus, and Middle East respiratory syndrome coronavirus (MERSCoV), and notably, severe acute respiratory syndrome coronavirus 2 (SARSCoV2) and its emerging variants.1,2Antibodybased therapy is now considered a viable therapeutic modality for infectious disease targets.3Polyclonal antibodies (pAb) isolated from hyperimmunized host serum are critical antibody pools from different B cells that detect different epitopes on the target protein or antigen. Poly clonality of pAbs permits many antigenic determinants of the target to be bound. This allows pAbs to be more sensitive in certain assays against a variety of target proteins, cells, or organisms and are more likely to result in highavidity binding, with a low risk of antigen escape variants emerging.4Currently, there are seven human polyclonal immunoglobulins (Igs) products.5Human polyclonal antibodies (hpAbs) or human immunoglobulins (hIgs) derived from the plasma of healthy and convalescing human donors, or hyperimmunized animals have been approved against various viral/bacterial infections, such as a respiratory syncytial virus (RSV).5hIgG is the most effective and is a lifesaving tool in medical emergency crises, such as severe acute respiratory syndrome (SARS) or the MERSCoV outbreaks, for which no appropriate treatment is available6,7,8and, recently, also for COVID19 caused by SARSCoV2.9,10,11,12,13,14The administration of human intravenous immunoglobulin (IVIg), monoclonal antibodies (mAbs), and animalderived pAbs are examples of current immunotherapy technology. Using current hpAbs products DPH has several limitations, including the need for large amounts of plasma from convalescent human donors with high titers to make the commercial product15,16and the scarcity of serum from convalescent human donors containing hpAbs. mAbs have the disadvantage of being directed against a single epitope, making them vulnerable to the pathogen’s mutational escape.17,18,19The modification of epitopes such that they are not recognized by most DPH Nterminal domain (NTD) and receptorbinding domain (RBD)antibodies underpin viral immune evasion by altering local conformation, charge, and hydrophobic microenvironments.20Furthermore, the cost of producing mAb products is DPH exceedingly expensive.21So, hpAbs derived from transgenic animals may be a feasible alternative to human plasmaderived IVIg therapy.22,23The largescale production of hpAbs in the most commonly transgenic animal species, involving mice24and rabbits, is inappropriate because they have small body sizes. Since heterologous animalderived antibody products are foreign proteins in humans their reactogenicity is often high. That can cause severe allergic reactions (anaphylaxis),25,26serum sickness disease,27and may provide “xenosialitis.”28,29Serum IL22RA1 sickness,27,30,31and type III.
