Genetic evolution of classical swine fever virus under immune environments conditioned by genotype 1-based modified live virus vaccine

Abstract

Modified live vaccines (MLVs) based on genotype 1 strains, particularly C-strain, have been used to prevent and control classical swine fever virus (CSFV) worldwide. Nevertheless, a shift in the predominant CSFV strains circulating in the field from genotype 1 or 3 to genotype 2 is seen. Genotype 2 is genetically distant from the vaccine strains and was recently reported during outbreaks after vaccine failure; this has raised concerns that vaccination has influenced viral evolution. In Korea in 2016, there was an unexpected CSF outbreak in a MLV-vaccinated commercial pig herd. The causative CSFV strain was genetically distinct from previously isolated Korean strains but similar to recent Chinese strains exhibiting enhanced capacity to escape neutralization; this suggests the need for global cooperative research on the evolution of CSFV. We analysed global E2 sequences, using bioinformatics tools, revealing the evolutionary pathways of CSFV. Classical swine fever virus genotypes 1 and 2 experienced different degrees and patterns of evolutionary growth. Whereas genotype 1 stayed relatively conserved over time, the genetic diversity of genotype 2 has progressively expanded, with few fluctuations. It was determined that genotype 2 evolved under lower immune pressures and at a higher evolutionary rate than genotype 1. Further, several selected codons, under diversifying selection in genotype 1 but under purifying selection in genotype 2, correspond to antigenic determinants, which could lead to evasion of vaccine-induced immunity. Our findings provide evidence that evolutionary changes in CSFV are the result of the disproportionate usage of the CSF MLVs in endemic areas; this underscores the need to develop mitigation strategies to minimize the substantial risk associated with the emergence of vaccine-escaping mutants.

In Vivo Demonstration of the Superior Replication and Infectivity of Genotype 2.1 with Respect to Genotype 3.4 of Classical Swine Fever Virus by Dual Infections

“…Antigenic variations among various genotypes of CSFVs certainly render the currently available vaccines more effective in neutralizing historical viruses, while allowing the newly invading virus to escape. This hypothesis has been amply addressed in several previous studies [20][21][22][23]. The neutralizing antibodies of co-infected with Ab pigs against the LPC/AHRI strain were higher than those against the TD/96 strain and the 94.4 strain.…”

Quasispecies dynamics in disease prevention and control

“…These events in the case of vaccines used in veterinary medicine are particularly significant because they may alter the cell tropism and host range of viruses, thus increasing the possibilities of their zoonotic transmission into humans (Schat and Baranowski, 2007). Evidence of vaccination-induced DNA and RNA virus evolution is increasing, and it has been documented with bovine respiratory syncytial virus, bovine herpesvirus-1, Marek's disease virus, porcine circovirus 2, and classical swine fever virus, among others [(Valarcher et al, 2000;Muylkens et al, 2006;Ji et al, 2014;Kekarainen et al, 2014;Constans et al, 2015;Yoo et al, 2018); reviews in Gandon et al, 2003;Schat and Baranowski, 2007)]. The timing of dominance of CTL-escape mutants of the simian immunodeficiency virus (SIV) was influenced by vaccination, and the process could be analyzed by penetration into the mutant spectra of the relevant viral populations (Loh et al, 2008).…”

Challenges of influenza A viruses in humans and animals and current animal vaccines as an effective control measure

“…Consequently, the evolution of viral population into vaccine-escaping directions such as emergence of immune escaping mutants and change of dominant viral genotype occurs. Those phenomena have been observed both in avian virus [ 73 74 75 ] and SIVs [ 76 77 ] as well as in other viruses of industrial animals [ 78 79 80 81 ]. Incomplete vaccine coverage commonly observed in the fields also can be a critical contributor accelerating the evolution [ 82 ].…”