Advancements and challenges in porcine genetically engineered vaccines (review)

Due to the high rate of development of the pig breeding industry both in the Russian Federation and abroad, the veterinary industry requires vaccines are safe for humans and the environment. A number of limitations of live midified and inactivated vaccines, discussed in the review, give advantage to the development and implementation of genetically engineered vaccines. They are divided into two large groups: laboratory-attenuated vaccines obtained by modifying the genome of the pathogen, and recombinant vaccines. The latter include subunit vaccines based on recombinant proteins, as well as live vector, DNA, and RNA vaccines. Possible ways of modifying the genome of viruses by homologous recombination, using meganucleases, "zinc fingers" (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 technology are described (S.H. Khan, 2019; Fabricci M. et al., 2020; Mazloum A. c et al., 2023). The expression of recombinant proteins is becoming possible in various systems: bacterial, produced by Escherichia coli , baculovirus, synthesizing proteins in insect cell cultures, yeast using Saccharomyces cerevisiae and Pichia pastoris (M. Karbalaei et al., 2020). The introduction of vector-based vaccines based on heterologous viruses (human adenovirus 5, avirulent herpesviruses, etc.) will help solve the problem of local and cell-mediated immunity to pathogens (J.L. Palgen et al., 2021). The main limiting factor in the use of DNA and RNA vaccines is the lack of a highly efficient method of delivering genetic material to target cells (T. Lee et al., 2022). Despite all the advantages of genetically engineered vaccines, their development, production and introduction into veterinary practice are limited due to the high cost, insufficient affinity and avidity of virus neutralizing antibodies, low antibody titer, and incomplete protection of animals during challenging. Despite the shortcomings, the development and registration of genetically engineered vaccines against infectious diseases of pigs in the world continues. Thus, the review presents and discusses existing developments and registered vaccines against African swine fever (M.V. Borca et al., 2020), pseudorabies (X. Liang et al., 2016), classical swine fever (S. Blome et al., 2017), porcine parvovirus (B. Garcia-Morante et al., 2020), coronavirus (X. Yuan et al., 2015) and circovirus (C. Park et al., 2017), porcine reproductive and respiratory syndrome (J. Cui et al., 2020). It is concluded that genetically modified viruses with a deficiency of genes encoding virulence factors are the most promising for the prevention of African swine fever, pseudorabies and porcine reproductive and respiratory syndrome. Subunit vaccines provide enhanced immunity against porcine parvovirus and circovirus. In turn, the possibilities of vector vaccines are most feasible in the fight against classical swine fever and porcine coronaviruses. In addition, the importance of genetically engineered vaccines lies in the formation of group immunity of swine populations to infectious diseases of viral etiology, and in the implementation of a strategy for differentiating infected from vaccinated animals (DIVA).