Efficacy and impact of current commercial porcine circovirus type 2 (PCV2) vaccines in dams and growing pigs

Porcine circovirus (PCV) was initially described as a contaminant of the continuous porcine kidney cell line PK-15 in 1974 (Tischer et al., 1974). It is a covalently closed single-stranded DNA virus belonging to the genus Circovirus in the family Circoviridae (Tischer et al., 1982). In early studies it was determined that PCV is ubiquitous, but non-pathogenic (Tischer et al., 1986). In 1991, a severe wasting disorder was observed in pigs shortly after weaning in western Canada (Harding et al., 1997; Clark, 1997), the United States (Allan et al., 1998b), and Europe (LeCann et al., 1997; Allan et al., 1998b). Although PCV was identified in tissues from affected pigs, it was determined to differ from the original PCV genome by 24% to 32% (Meehan et al., 1998; Cheung et al., 2007). This led to classification of PCV into two distinct genotypes: the original non-pathogenic strain or PCV type 1 (PCV1) and the newly isolated, pathogenic strain or PCV type 2 (PCV2) (Meehan et al., 1998). Further genomic alignments revealed that PCV2 could be separated into two distinct groups: group 1 comprised of three distinct clusters (1A to 1C), and group 2 comprised of five distinct clusters (2A to 2E) (Olvera et al., 2007). Due to multiple designations for these groups (de Boisseson C. et al., 2004; Olvera et al., 2007; Timmusk et al., 2008; Grau-Roma et al., 2008; Carman et al., 2008), use of lower case letter designations for each group was proposed by Segalés et al. (2008) for uniformity, resulting PCV2 group 1 becoming PCV2a and PCV2 group 2 becoming PCV2b (Segalés et al., 2008).\nSince its original identification as the etiological agent of postweaning multisystemic wasting syndrome (PMWS) (Ellis et al., 1998; Meehan et al., 1998; Allan et al., 1998a), PCV2 has been associated with multiple disease manifestations, collectively referred to as PCV-associated disease (PCVAD) (Opriessnig et al., 2007). Besides PMWS (Clark, 1997; Harding et al., 1998), these disease manifestations include respiratory disease (Kim et al., 2003), enteric disease (Kim et al., 2004), reproductive failure (West et al., 1999), and porcine dermatitis and nephropathy syndrome (PDNS) (Choi et al., 2001). All are considered of high economic importance due to their contribution to ill-thriftiness, morbidity rates varying between 12.5% and 59% (USDA, 2008), and variable mortality rates (López-Soria et al., 2005; Calsamiglia et al., 2007; Alarcon et al., 2011; Grau-Roma et al., 2012).\nPCV2 is considered ubiquitous and is prevalent globally (Tischer et al., 1986; Dulac et al., 1989; Edwards et al., 1994; Allan et al., 2000; Walker et al., 2000; Zhou et al., 2006; Segalés et al., 2008) due to both its resilience to inactivation methods (Allan et al., 1994; Welch et al., 2006; O'Dea et al., 2008) and its numerous methods of transmission. These include horizontal transmission routes such as colostrum (Shibata et al., 2006), feces (Shibata et al., 2003), invertebrate vectors (Blunt et al., 2011), nasal secretions (Shibata et al., 2003), oral secretions (Shibata et al., 2003), and seminal fluids (Larochelle et al., 2000). Vertical transmission routes include either early crossing of the zona pellucida resulting in oocyte infection (Bielanski et al., 2004; Mateusen et al., 2004) or intrauterine fetal infection during dam viremia (West et al., 1999; O'Connor et al., 2001; Ladekjær-Mikkelsen et al., 2001; Nielsen et al., 2004; Park et al., 2005; Madson et al., 2009b).\nIn response to a large outbreak of PCVAD in late 2005 (Cheung et al., 2007), which coincided with a global shift of PCV2a towards PCV2b (Cheung et al., 2007; Gagnon et al., 2007; Olvera et al., 2007; Segalés et al., 2008), PCV2 vaccines were introduced on the North American market in 2006. To date, there are five commercially available vaccines, four of which are licensed for use in the United States by the United States Department of Agriculture. These vaccines use three different methods of antigen delivery, all are licensed for use in weaning age pigs, and one is additionally licensed for use in breeding dams. The first developed vaccine, Circovac® (Merial Inc.), was experimentally launched in 2004 (Reynaud et al., 2004a, 2004b) and was initially only available in France and Germany under special license (Charreyre et al., 2005), but was globally licensed in late 2007 (Burch, 2008). Circovac® is based on an inactivated PCV2a, and is unique that it is licensed for both weaning age piglets and breeding dams. It is currently licensed for use in the US, but is not commercially available. FosteraTM PCV (Pfizer Animal Health Inc.) is a reformulated version of Suvaxyn® PCV (Fort Dodge Animal Health Inc.), and was launched in North America in 2011 after Suvaxyn® PCV was voluntarily removed from the market in May 2010 in response to concerns of improper inactivation (Gagnon et al., 2010). FosteraTM PCV is based on an inactivated chimeric virus in which the capsid gene of PCV2a is cloned into the non-pathogenic backbone of PCV1 (Fenaux et al., 2004) which has been demonstrated to be attenuated in vivo (Fenaux et al., 2003). FosteraTM PCV is used as a single dose in weaning age pigs. The remaining three vaccines are all based on ORF2 protein expressed in a baculovirus vector system (Beach et al., 2012). Ingelvac® CircoFLEXTM (Boehringer Ingelheim Vetmedica Inc.) is administered as a single dose to weaning age pigs while Circumvent® PCV (Merck Inc.) is administered as two doses at weaning and two weeks later. Both vaccines are licensed for use and commercially available in the US. Porcilis® PCV (MSD Inc.) is administered as a single dose at weaning and is not currently available in the US.\nWithin the PCV2 literature, there have only been two peer-reviewed meta-analyses; one on experimental trials with PCV2 (Tomás et al., 2008) and the other on general efficacy of PCV2 vaccines (Kristensen et al., 2011). Furthermore, there have also been three meta-analyses presented at conferences, which focused solely on the performance of Ingelvac® CircoFLEXTM (Holck et al., 2010; Diaz et al., 2010; Coll et al., 2010). Thus, our first study, a pairwise meta-analysis of the commercially available PCV2 vaccines in the United States, was performed using previous literature through a critical review and comparing the efficacy of the vaccines compared to no vaccine administration.\nIn the US, PCV2 vaccination is currently only licensed for use in pigs at 21 days of age or older. However, producers commonly vaccinate piglets against PCV2 during routine processing of piglets, including teeth clipping, tail docking, castration, and iron administration which occurs within the first few days of life (Marchant-Forde et al., 2009), in an attempt to minimize handling and stress. Thus, the main objective of our second study was to compare two commercially available vaccines, and their efficacy in 5-day-old and 21-day-old piglets.\nRecently, much attention has been given to the role of dam vaccination and vertical transmission of PCV2 (Madson et al., 2009a; Madson et al., 2009c; Madson et al., 2011; Kurmann et al., 2011). Furthermore, a recent field study across North America demonstrated a 44.8% (226/504) prevalence of PCV2 viremia in neonatal piglets with a large portion of the piglets appearing normal and healthy (Shen et al., 2010). To further characterize the role of dam PCV2 vaccination in newborn piglet viremia, our third study focused on extra-label use of a commercial available piglet vaccine in breeding females. Randomly selected dams were vaccinated with the PCV2 vaccine prior to insemination or left unvaccinated. At parturition, blood samples were collected from five healthy, randomly-selected piglets from each litter and colostrum was collected from the dam to determine if vaccination of the dam reduces the presence of PCV2 in the colostrum and the offspring.