Similarity of European porcine reproductive and respiratory syndrome virus strains to vaccine strain is not necessarily predictive of the degree of protective immunity conferred

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Abstract

The objective of this study was to determine the degree of protection conferred by a Lelystad-like modified live virus (MLV) vaccine against a heterologous wild-type porcine reproductive and respiratory syndrome virus (PRRSV) isolate of the same cluster. For this purpose, fourteen 3-week-old piglets were divided into three groups: Group A pigs were vaccinated with a modified live virus vaccine, Group B pigs were used as positive controls, and Group C pigs as negative controls. Twenty-eight days after the last dose of vaccine, all pigs in Groups A and B were inoculated with the Spanish PRRSV strain 5710. To evaluate efficacy, clinical signs were recorded and the presence of challenge virus was determined by virus isolation in blood samples and nasal swabs collected at various time points post-challenge (p.c.) and in tissue samples collected at necropsy 24 days p.c.

After challenge, moderate clinical signs were observed in pigs from Groups A and B. In addition, all vaccinated pigs were viremic at least once, although viremia tended to be more sporadic in this group than in Group B pigs. PRRSV was detected in at least one tissue sample from four out of five pigs from Group A and in all pigs from Group B. The results indicate that the protection conferred by the MLV vaccine used in this study against a closely related virulent strain was only partial. The findings suggest that the degree of genetic homology of ORF5 between MLV vaccine and challenge isolate is not a good predictor of vaccine efficacy.

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is an economically significant disease of pigs (Rossow, 1998). The causal agent, PRRS virus (PRRSV), is a small RNA virus of the Arteriviridae family (Cavanagh, 1997). Although, in general, PRRS is clinically similar in North America and Europe, the respective strains differ in virulence (Halbur et al., 1996) and in antigenic (Bautista et al., 1993, Nelson et al., 1993) and genetic (Meng et al., 1995) properties. This heterogeneity is likely to be one of the principal obstacles to effective prevention and control of the disease using commercial vaccines (Meng, 2000).

Pigs naturally infected with PRRSV develop strong homologous immunity preventing re-infection with the same strain (Lager and Mengeling, 1997, Lager et al., 1997, Lager et al., 1999, Nielsen et al., 1997, Mengeling et al., 2003). Protective immunity has also been observed with modified live virus (MLV) and inactivated virus vaccines when the parent virus strain used to produce the vaccine was used for the challenge (Hesse et al., 1996, Gorcyca et al., 1997, Plana-Duran et al., 1997). However, naturally immunized pigs seem to be inconsistently and less completely protected against challenge with heterologous strains (Lager et al., 1999, Mengeling et al., 1999). Similar results have been obtained with gilts immunized with American MLV vaccines and challenged with a heterologous American strain of PRRSV (Gorcyca et al., 1997, Osorio et al., 1998) and with growing pigs immunized with European MLV vaccines and then challenged with a heterologous American strain of PRRSV (van Woensel et al., 1998, Labarque et al., 2003).

These results suggest that the degree of protection afforded by the vaccination of susceptible pigs depends on the degree of similarity between the PRRSV-vaccine strain and the field strain to which the pigs are exposed. Until recently, it was thought that vaccines based on European strains would provide effective protection against any wild-type strain circulating in Europe. However, the discovery of genetic diversity among European strains (Forsberg et al., 2002, Stadejek et al., 2002) and the identification of the three major clusters of field isolates, namely a cluster of Lelystad-like isolates, a cluster of purely Danish isolates, and a cluster of highly diverse Italian-like isolates (Forsberg et al., 2002), highlight the importance of assessing the efficacy of current European-type vaccines based on viruses belonging to the Lelystad-like cluster against the genetically diverse European clusters. Labarque et al. (2004) and Scortti et al. (2006) have shown that the efficacy of European-type MLV vaccines against strains of a different genetic cluster is only partial. Nonetheless, it is assumed that these products would provide good protection against heterologous isolates of the same genomic cluster, based on the genomic similarity between them, with the assumption that viruses that are closely related genetically will be also related antigenically. However, little is known about the correlation between genomic and antigenic properties.

Therefore, the objective of the present study was to determine the degree of protection conferred by a Lelystad-like MLV vaccine against a heterologous wild-type isolate of the same cluster.

Section snippets

Animals and facilities

Fourteen 3-week-old crossbred piglets from a herd free of PRRSV and with no measurable PRRSV serum antibody titres were randomly assigned to groups of four to five animals and housed in isolation in pens with a concrete floor and an automatic watering system. This study was approved by the Animal Ethics Committee of the Complutense University, Madrid (Spain).

Vaccine, virus and cell cultures

The MLV vaccine used (Porcilis® PRRS, Intervet Laboratories) is based on the Lelystad-like cluster of European PRRSV strains. The parent

Clinical signs

No adverse reactions to vaccination were noted and pigs from all experimental groups remained in good health until experimental inoculation with virulent PRRSV. After challenge, moderate clinical signs were observed in the pigs from Groups A and B. Specifically, most pigs from Group A showed a slight increase in rectal temperature from day 3 to day 5 post-inoculation (p.i.). In addition, depression was recorded for pig No. 1 on day 3 p.i. and for pig No. 3 on days 3 and 4 p.i. Finally, pig No.

Discussion

The impact of PRRSV on pig production has stimulated the development of various types of vaccines for controlling disease, both in growing pigs and in breeding females. Decisions on whether to use MLV vaccines to control PRRSV in growing pigs are sometimes based on the degree of ORF-5 homology between a field strain and commercially available vaccines. Therefore, we investigated the ability of one commercially available attenuated PRRSV vaccine, belonging to the Lelystad cluster, to confer

Acknowledgements

This study was supported by grant no. AGL2001-2055 from the Spanish CICYT. Esther Álvarez was supported by a fellowship of the Spanish CICYT.

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