INTRODUCTION
The livestock industry has grown up swiftly from the last decade and earned $1.4 trillion annually (Sohaib and Jamil 2017). This industry is continuously evolving due to rapidly increasing demand of livestock products. Therefore, use of veterinary drugs is essential for therapeutic and prophylactic purposes in livestock production to improve growth, productivity, and food safety (Falowo and Akimoladun 2019). Only one segment of this sector i.e., meat production valued at 838.3 billion U.S. dollars in 2020 and forecasted to increase to 1157.6 billion U.S. dollars by 2025. These drugs are globally utilized to enhance the profitability and productivity of modern food animal production by facilitating higher animal densities, earlier weaning, meat quality, cheaper feeds, and carcass yield (Moreno and Lanusse 2017). These life-saving agents include a broad range of natural, synthetic, and semi-synthetic compounds such as, antibiotics, antiparasitics, β-agonist and vaccines (Moreno and Lanusse 2017). Among the antibiotics used in livestock production, commonly consumed are amprolium, penicillin, tetracyclines, streptomycin, tylosin, sulphonamides, aminoglycosides, β-lactams, quinolones macrolides and lincosamides (Landoni and Albarellos 2015; Alhaji et al. 2018) while antiparasitic drugs include anthelmintics or coccidiostats such as stilbenes, nitrofurans, amphenicols, nitroimidazoles, pyrethroids, carbamates and sedatives (Falowo and Akimoladun 2019). The extensive use of antimicrobial agents leads to continuously increasing antimicrobial resistance. Mostly, scientists believe that improper and immense administration of antimicrobials is a single most significant factor that is responsible for emergence of resistance (Hoelzer et al. 2017). The veterinary researchers have identified that intestinal microbiome of food producing animals can act as a reservoir of resistant bacteria in the society (Graveland 2011; Patchanee 2014; Moradigaravand et al. 2017). However, there is high risk of multi-drug resistant bacterial zoonosis and pose a serious threat to the public health (Zhu et al. 2013; Jans et al. 2017; Lugsomya et al. 2018). At present, the average annual utilization of antimicrobial compounds per-kilogram of animal produced is approximately at >100mg/kg worldwide (Vishnuraj et al. 2016). It has been estimated that almost 80% of the antibiotics consumed in veterinary field are growth promoters, which mostly exceed the amount of total antibiotic consumption in human medical care (Vishnuraj et al. 2016). The antibiotic residues in edible animal products have increased beyond the acceptable level in most of developing countries (Use, 2017). Moreover, many scientific reports revealed that consistently use of antimicrobial agents in enormous amount result in deposition of drug residues in different organs and muscles of animals (Sanz et al., 2015). These residues in edible animal products can cause severe health risks to humans when ingested (Use, 2017). The development of antimicrobial resistance and hypersensitivity reactions are most common outcome in humans (Use, 2017). Dawn of Recombinant Therapeutics The recombinant proteins are gaining much attention worldwide due to its variety of applications. Efficient strategies are utilized to produce high quality proteins in enormous amount with low cost (Palomares et al. 2004). The potential of engineered recombinant proteins are widely explored for the development of therapeutic and prophylactic use (Gifre et al. 2017). These include antibodies, enzymes, cytokines, growth factors and vaccines (Schillberg et al. 2019). These proteins are synthesized in various expression systems depending upon the type of protein. Commonly used expression systems are bacteria, yeast, filamentous fungi, and unicellular algae (Legastelois et al. 2017; Owczarek et al. 2019). All expression systems have their own merits and demerits, and its selection depends upon the protein of interest to be expressed, such as, eukaryotic protein modifications are only possible in eukaryotic expression system because prokaryotic system does not support these modifications (Rai and Padh 2001). Moreover, cell free expression systems are now attracting the attention of scientific community to be utilized for the fast synthesis of recombinant proteins with eliminating the processes of purification (Swiech et al. 2012).
These proteins are widely utilized due to its dynamic properties. The gene encoding the particular protein is isolated from the respective organism and synthesized in various expression systems. Thereafter, same protein is again injected in the living body e.g., insulin. Therapeutic proteins minimize the issues related to the synthetic and semi-synthetic drugs e.g., antibiotic associated diarrhea, unpleasant taste and reduce absorption from the gut. Appropriate modifications are required to increase specificity, to prolong half-life, and to improve functionality (Gupta et al. 2017). The continuous impressive work by the scientists in the recombinant protein technology have brought multiple therapeutic proteins into clinical applications (Kim et al. 2017). Due to these advancements, demand of recombinant proteins is increasing in the livestock sector as well.
Different Ranks of the Recombinant Therapeutics
Vaccines are very successful method for disease prophylaxis in humans and animals. Most deadly diseases are cured today through the conventional and modern vaccines which significantly decrease the graph of diseases in livestock (Jorge and Dellagostin 2017). Majority of conventional vaccines today in market include live attenuated vaccines, killed vaccines, inactivated vaccines, toxoids and cell membrane compounds (McVey and Shi 2010; Unnikrishnan et al. 2012). Attenuated vaccines are very effective in stimulation of immune response both humoral and cell mediated (Rizzi et al. 2012; da Costa et al. 2015). However, killed and inactivated vaccines are preferred over the attenuated vaccines due to its safety profile in the animal body, but they are less effective to elicit the immune response in the host along with its adverse effects (Cho et al. 2002; Moreira et al. 2016). The main problem associated with the attenuated vaccines is its reversion back to its virulent form after inoculation into the body (Shimoji et al. 2002; Unnikrishnan et al. 2012). Toxoid vaccines are raised against lethal and fatal bacterial and mycotoxins after inactivation through chemical agents (Arimitsu et al. 2004). Toxoids are effective in a sense that these induce reliable humoral immune response but negligible cell-mediated immune response (Jorge and Dellagostin 2017). The widespread use of these prophylactic agents prominently improves animal health. Although, multiple bacterial and viral diseases in animals are efficiently treated with conventional vaccines but they are still expensive to produce and require administration of multiple doses to achieve optimal immune response (Meeusen et al. 2007; Delany et al. 2014). Therefore, it is the necessity of the time to introduce the more immunogenic, safer and economical vaccines, which are more capable to efficiently control and eradicate the animal diseases.
The advancements in next generation sequence technologiesand understanding the molecular mechanisms of pathogenesis of various pathogens resulted in the introduction of recombinant veterinary vaccines in the market (Jorge and Dellagostin 2017). It enables the genome and proteome screening with the aid of next generation technologies, which prominently enhance the chances of more appropriate antigen discovery.