Location: Virus and Prion Research
Project Number: 5030-32000-118-05-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 25, 2014
End Date: Sep 30, 2018
Our objective is to determine the frequencies of B/T lymphocytes and antibody-secreting cells (ASC) trafficking from the gut into blood and to the mammary gland in response to porcine epidemic diarrhea virus (PEDV) stimulation in gilts at different gestational ages and lactation. We will assess if their frequencies correlate with IgA PEDV antibodies in milk and passive protection in suckling piglets. Our findings will provide insight into which immune markers in blood could be used as a correlate of mucosal homing and PEDV immunity in the intestine/mammary gland and lactogenic immunity to PEDV in suckling piglets. This assay could provide a surrogate measure and rapid assessment of PEDV gut stimulation and lactogenic immunity in field-exposed or vaccinated gilts.
Newborn piglets are born agammaglobulinic and are highly susceptible to a plethora of infectious agents. Porcine epidemic diarrhea virus (PEDV) causes 80-100% morbidity and mortality in seronegative newborn piglets. Since PEDV first appeared in the United States in 2013, the virus has spread to 30 states, killing approximately 7 million piglets. Due to the high virulence of PEDV and the naïve, immature immune system of the neonatal suckling piglet, passive lactogenic immunity to PEDV is critical for piglet protection induced via the gut-mammary gland-secretory IgA (sIgA) axis. However, the stage of pregnancy and dose required to stimulate immunity in gilt/sow lactogenic secretions remains elusive. Additionally, various reports by producers and veterinarians suggest limited or no protection in suckling piglets from PEDV-positive animals following feedback methods, despite using aggressive feedback procedures. These field observations highlight the need for immunological correlates of lactogenic immunity in gilts/sows and passive protection in suckling piglets. We hypothesize that: 1) the frequencies of lymphocytes and PEDV-specific antibody-secreting cells (ASC) trafficking from the gut, into blood, and to the mammary gland in response to PEDV stimulation will correlate with the amount of PEDV IgA antibodies in colostrum and milk and subsequent passive protection in suckling piglets; and 2) the lymphocyte and ASC frequencies during trafficking via blood will provide a surrogate measure of PEDV gut stimulation efficiency and lactogenic immunity in the field. In this project, we will measure B/T lymphocytes and PEDV-specific IgA+ ASC (and their adhesion molecules/chemokines) in the gut, mammary gland, and blood after oral PEDV inoculation of pregnant gilts at various gestational stages. We will determine if theses parameters correlate with IgA antibodies in milk and passive protection of suckling piglets after PEDV challenge. This research is for scientists to collaborate on in vivo and in vitro characterization of lymphocytes and ASC trafficking from the gut into blood and to the mammary gland and subsequent immune protection of suckling piglets. To study lactogenic immunity in pregnant swine and passive protection in suckling neonates in response to oral PEDV inoculation, the research will be completed in three phases: 1) Cooperator will analyze the effect of stage of pregnancy by orally inoculating gilts with PEDV during different trimesters; 2) Cooperator (if time and funding permit) will analyze the effect of parity by oral PEDV inoculation in primiparous vs multiparous animals; and 3) ARS will use the information garnered from these studies to determine correlates of lactogenic immunity in gilts/sows exposed to PEDV in the field.