Location: Virus and Prion ResearchTitle: Antibody repertoire development in fetal and neonatal piglets. XXIII: fetal piglets infected with a vaccine strain of PRRS virus display the same immune dysregulation seen in isolator piglets) Author
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2012
Publication Date: 5/21/2012
Citation: Sun, X.Z., Wertz, N., Lager, K.M., Tobin, G., Butler, J.E. 2012. Antibody repertoire development in fetal and neonatal piglets. XXIII: fetal piglets infected with a vaccine strain of PRRS virus display the same immune dysregulation seen in isolator piglets. Vaccine. 30(24):3646-3652. Interpretive Summary: Porcine reproductive and respiratory syndrome is a disease that affects swine worldwide resulting in significant economic losses. It is caused by a virus (PRRSV) that was discovered in 1991. Although vaccines are now available, they can have limited efficacy. Why this occurs is not understood, but it must be related to how the virus interacts with the pig and how this interaction affects the pig's immune response against PRRSV infection. This paper reports studies evaluating the basic or molecular immune response of a pig against PRRSV. Previous work demonstrated that PRRSV can thwart or dysregulate the immune response in a germ-free pig model where pigs are housed in a sterile isolator. The isolator piglet model was used to evaluate the effect of the virus without any other confounding factors. Although this model provides insight into how a virus might affect a normal pig, the model is still artificial. Since PRRSV can cause fetal infection and eventual death, we conducted an experiment to characterize the fetal immune response to a PRRSV infection during late gestation, a stage of gestation when porcine fetuses can develop an immune response. Similar to the isolator pig model, PRRSV was able to dysregulate the immune response supporting previous isolator pig observations, and indicating that the effect of PRRSV on the immune system is valid and not just an artifact of the isolator pig model. This work provides insight into how the virus naturally interacts with the pig and can contribute to a better understanding of the immune response that may lead to improved vaccines.
Technical Abstract: The Ig levels and antibody repertoire diversification in fetal piglets infected with an attenuated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) were measured. Serum Ig levels were greatly elevated in PRRSV-infected fetuses; IgG was elevated >10-fold, IgM > 8-fold and IgA >2-fold compared to uninfected fetuses. Their IgM to IgG to IgA profile was the same as that in isolator piglets infected for the same period with wild-type PRRSV. However, they showed less repertoire diversification than even isolator piglets that were maintained germfree (GF). The repertoire diversification index (RDI) for PRRSV-infected isolator piglets was 10-fold higher and comparable to littermates infected with swine influenza (S-FLU). However when expressed as the RDI:Ig ratio, infected fetuses appeared 10-fold less capable of repertoire diversification than uninfected littermates and GF isolator piglets. Compared to S-FLU isolator piglets that resolve the infection, the RDI:Ig of PRRSV-infected isolator piglets was 100-fold lower. Overall, infection of fetuses with an attenuated virus shows the same immune dysregulation seen postnatally in wild type infected isolator piglets, indicating that: (a) attenuation did not alter the ability of the virus to cause dysregulation and (b) the isolator infection model reflects the fetal disease.