Systematic review and meta-analysis on efficacy of Fostera PRRSV Modified Live Virus vaccine studies in growing pigs
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important health challenges that currently exists in the global swine industry. PRRSV is an enveloped, single-stranded, positive-sense RNA virus belonging to genus Arterivirus. A PRRSV infection is clinically characterized by reproductive failure in sows and/or respiratory disease in growing pigs, causing significant economic losses (Zimmerman et al., 2012). RNA viruses have relatively high mutation rates compared to DNA viruses, mainly due to the low fidelity of viral RNA-dependent RNA polymerases (Arnold et al., 2005; Vignuzzi et al., 2008). This rapid high mutation rate usually leads to the generation of genetically and antigenically variable virus strains in the field, which can hinder the development of effective vaccines. PRRSV is currently classified into two distinct genotypes, type 1 and type 2 which differs significantly in term of their clinical, and genetic properties (Kapur et al., 1996; Labarque et al., 2004; Nelson et al., 1993). Within type 2, it has been proposed a further subdivision into 9 genetic lineages (Shi et al., 2010). The extensive heterogeneity of PRRSV presents challenges for the efficacy vaccines, which are currently based on a single virus strain. Consequently, the current commercially vaccines confer partial cross-protection against heterologous PRRSV strains (Kimman et al., 2009; Li et al., 2014; Murtaugh and Genzow, 2011), which is sufficient to significantly decrease duration and magnitude of viremia, shedding, and lung lesions. In previous cross-protection studies, type 2 PRRSV modified live vaccine have not been effective when applied to control pigs against type 1 PRRSV (Labarque et al., 2003; van Woensel et al., 1998; Labarque et al., 2000). Cross-protection discoursed by type 2 PRRSV vaccine against type 1 PRRSV is an important clinical issue in many Asian countries because of the emergence of type 1 PRRSV (Chen et al., 2011; Nam et al., 2009; Thanawongnuwech et al., 2004). A modified live type 2 PRRSV vaccine (Fostera PRRS, Zoetis, Parsippany, NJ, USA) was introduced in the US in 2012, and is profess to be efficacious to protect pigs against heterologous type 2 PRRSV challenge (Park et al., 2014), and has been licensed to produce better cross-protection against heterologous PRRSV challenge. Fostera PRRS is an attenuated PRRSV vaccine, passaged first on pig kidney cells engineered to constitutively express the porcine CD163 PRRS receptor, then on baby hamster kidney cells that were also engineered to express porcine CD163. The commercial modified live PRRS vaccines were attenuated by passage on African green monkey kidney cells (cell line MA-104 and derivatives), which inappropriately express the macrophage-specific CD163 PRRS receptor. Adaptation of the virus to use the monkey CD163 receptor contributes to the observed attenuation phenotype of at least some of these vaccines, namely a reduced ability of the vaccine virus to infect the host target cell, primary porcine alveolar macrophages (Pearce et al., 2014). In contrast, the Fostera PRRSv is passaged only on cells expressing porcine CD163, and thus potentially maintaining its ability to replicate to high titer on primary porcine alveolar macrophages. This fundamental difference in attenuation may play a role in the dynamics of viremia in pigs, following challenge with PRRS viruses from genotypes 1 (Charoenchanikran et al., 2016; Choi et al., 2016; Do et al., 2015; Park et al., 2015, 2014; Savard et al., 2016; Tian et al., 2015).