R. A. Patterson

Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

Abstract Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used modified live virus PRRS vaccine (PRRS-MLV) against genetically divergent PRRSV strains remains questionable. Therefore, we evaluated an alternate and proven mucosal immunization approach by intranasal delivery of PRRS-MLV (strain VR2332) with a potent adjuvant to elicit cross-protective immunity against a heterologous PRRSV (strain MN184). Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was chosen as a potent mucosal adjuvant due to its Th1 biased immune response to PRRS-MLV. Unvaccinated pigs challenged with MN184 had clinical PRRS with severe lung pathology; however, vaccinated (PRRS-MLV+ Mtb WCL) pigs challenged with MN184 were apparently healthy. There was a significant increase in the body weight gain in vaccinated compared to unvaccinated PRRSV challenged pigs. Vaccinated compared to unvaccinated, virus-challenged pigs had reduced lung pathology associated with enhanced PRRSV neutralizing antibody titers and reduced viremia. Immunologically, an increased frequency of Th cells, Th/memory cells, γδ T cells, dendritic cells, and activated Th cells and a reduced frequency of T-regulatory cells were detected at both mucosal and systemic sites. Further, reduced secretion of immunosuppressive cytokines (IL-10 and TGF-β) and upregulation of the Th1 cytokine IFN-γ in blood and lungs were detected in mucosally vaccinated, PRRSV-challenged pigs. In conclusion, intranasal immunization of pigs with PRRS-MLV administered with Mtb WCL generated effective cross-protective immunity against PRRSV.

Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs

Abstract Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease to pork producers worldwide. Commercially, both live and killed PRRSV vaccines are available to control PRRS, but they are not always successful. Based on the results of mucosal immunization studies in other viral models, a good mucosal vaccine may be an effective way to elicit protective immunity to control PRRS outbreaks. In the present study, mucosal adjuvanticity of Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was evaluated in pigs administered a modified live PRRS virus vaccine (PRRS-MLV) intranasally. A Mtb WCL mediated increase in the frequency of NK cells, CD8+and CD4+ T cells, and γδ T cells in pig lungs were detected. Importantly, an increased and early generation of PRRSV specific neutralizing antibodies were detected in PRRS-MLV+ Mtb WCL compared to pigs inoculated with vaccine alone. In addition, there was an increased secretion of Th1 cytokines (IFNγ and IL-12) that correlated with a reciprocal reduction in the production of immunosuppressive cytokines (IL-10 and TGFβ) as well as T-regulatory cells in pigs vaccinated with PRRS-MLV+ Mtb WCL. Further, a complete rescue in arginase levels in the lungs mediated through Mtb WCL was observed in pigs inoculated with PRRS-MLV. In conclusion, Mtb WCL may be a potent mucosal adjuvant for PRRS-MLV in order to potentiate the anti-PRRSV specific immune responses to control PRRS effectively.

Genetics of Growth and Reproduction in the Turkey. 17. Changes in Genetic Parameters Over Forty Generations of Selection for Increased Sixteen-Week Body Weight

A line (F) of turkeys was selected over 40 generations for increased 16-wk BW. The base population for the F line was a randombred control population that was maintained without conscious selection and used to remove yearly environmental variation in the F line. Selection was effective in increasing 16-wk BW in the F line. Selection differentials based on the mean of the selected parents minus the mean of the entire population (intended) and intended selection differentials weighted for number of offspring produced (actual) did not differ consistently, indicating that natural selection was not opposing artificial selection during the reproduction of the F line. The realized heritability of 16-wk BW in the F line, based on the linear regression of the selection response on accumulated actual selection differential, declined with selection. For both sexes combined, the realized heritability was 0.309 +/- 0.022 (SE), 0.268 +/- 0.033, 0.268 +/- 0.026, 0.166 +/- 0.016, and 0.242 +/- 0.004, respectively, for generations 1 to 10, 11 to 20, 21 to 30, 31 to 40, and 1 to 40. Genetic increases in 16-wk BW in the F line over 40 generations of selection were positively associated with BW at other ages (8 and 20 wk of age and at 50% production), shank length and width at 16 wk of age, days from stimulatory lighting to production of the first egg, and egg weight but were negatively associated with egg production, intensity of lay (maximum and average clutch length and rate of lay), and walking ability. Over the 40 generations of selection, genetic increases in BW in the F line were not associated with changes in broodiness or mortality to 8 wk of age. During generations 31 to 40, BW at 8 and 20 wk of age continued to increase in the F line, but there was no significant change in adult BW, and the only significant change in reproduction traits was for average clutch length (-0.030). Because the genetic changes in some correlated traits were not consistent in all generation intervals studied, the genetic correlation between the selected trait (16-wk BW) and the correlated trait apparently changed with selection.

Porcine reproductive and respiratory syndrome virus induces pronounced immune modulatory responses at mucosal tissues in the parental vaccine strain VR2332 infected pigs

Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs caused by PRRS virus (PRRSV). The PRRSV VR2332 is the prototype North American parental strain commonly used in the preparation of vaccines. Goal of this study was to understand missing information on VR2332 induced immune modulation at the lungs and lymphoid tissues, the sites of PRRSV replication. Pigs were infected intranasally and samples collected at post-infection day (PID) 15, 30, and 60. Microscopically, lungs had moderate interstitial pneumonia, and the virus was detected in all the tested tissues. Peak antibody response and the cytokine IFN-γ secretion were detected at PID 30, with increased TGF-β until PID 60. Population of CD8(+), CD4(+), and CD4(+)CD8(+)T cells, Natural killer (NK) cells, and γδ T cells in the lungs and lymphoid tissues were significantly modulated favoring PRRSV persistence. The NK cell-mediated cytotoxicity was significantly reduced in infected pigs. In addition, increased population of immunosuppressive T-regulatory cells (Tregs) and associated cytokines were also observed in VR2332 strain infected pigs.

Collagen characteristics and organization during the progression of cholesterol-induced atherosclerosis in Japanese quail.

This study reports the concentration of collagen and its hydroxypyridinoline crosslinks, collagen fibril organization in the dorsal aortas, and systolic blood pressure during the progression of atherosclerosis in Japanese quail selected for cholesterol-induced atherosclerosis. The quail were placed on either a control or 0.5% cholesterol-added diet at approximately 16 weeks of age. The concentration of total collagen did not change in the control arteries during the course of the study, whereas at 5 and 10 weeks of cholesterol feeding, collagen levels decreased in the cholesterol-fed birds. Hydroxypyridinoline concentration increased during the duration of the study in the cholesterol-fed birds and by 15 and 20 weeks of cholesterol feeding, levels were significantly increased over those observed in the control arteries. Transmission electron microscopy showed changes in the organization of collagen fibrils. Increased systolic blood pressure was noted beginning at 10 weeks of cholesterol feeding, which is suggestive of other systemic changes induced by hypercholesterolemia. These results demonstrated remodeling of the collagen component of the dorsal aorta extracellular matrix during the progression of atherosclerosis and are suggestive of other systemic cardiovascular system changes.