Lactogenic immunity and vaccines for porcine epidemic diarrhea virus (PEDV): Historical and current concepts

Abstract

Morbidity, mortality, and loss of productivity from enteric diseases in neonatal piglets cost swine producers millions of dollars annually. In 2013-2014, the porcine epidemic diarrhea virus (PEDV) outbreak led to $900 million to $1.8 billion in annual losses to US swine producers. Passive lactogenic immunity remains the most promising and effective way to protect neonatal suckling piglets from enteric diseases like PEDV. Protecting suckling piglets through lactogenic immunity is dependent on trafficking of pathogen-specific IgA plasmablasts to the mammary gland and accumulation of secretory IgA (sIgA) antibodies in milk, defined as the gut-mammary-sIgA axis. Due to an impermeable placenta, piglets are born agammaglobulinic, and are highly susceptible to a plethora of infectious agents. They rely solely on colostrum and milk antibodies for maternal lactogenic immunity. Previous advances in the development of live and attenuated vaccines for another devastating diarrheal virus of pigs, transmissible gastroenteritis virus (TGEV), provide insights into the mechanisms of maternal immunity and piglet protection. In this chapter, we will review previous research on TGEV-induced lactogenic immunity to provide a historical perspective on current efforts for PEDV control and vaccines in the swine industry. Identifying factors that influence lactogenic immunity and the gut-mammary-sIgA axis may lead to improved vaccine regimens for PEDV and other enteric pathogens in gestating swine and improved overall herd immunity, swine health and industry productivity.

Keywords: Gut-mammary-secretory IgA axis; Lactogenic immunity; Maternal antibodies; Porcine epidemic diarrhea virus; Swine; Transmissible gastroenteritis virus.

Fig. 1

Schematic to depict the gut-mammary-sIgA axis and trafficking molecules. Providing sufficient PEDV-specific immunity in colostrum/milk is dependent on trafficking of IgA plasmablasts (immature plasma cells) from the intestine to the mammary gland and accumulation of sIgA antibodies in milk. Trafficking of lymphocytes to mucosal tissues is largely regulated by α4β7 interacting with MAdCAM-1 and CCR9/10 interacting with CCL25/28 while trafficking to systemic sites is regulated by α4β1 and L-selection interacting with VCAM-1 and PNAd, respectively. Adapted from (Chattha et al., 2015).

Fig. 2

A–C. Gilt and piglet fecal PEDV RNA shedding post-PEDV exposure and piglet diarrhea scores post-challenge. (A) PEDV RNA fecal titers were highest post-inoculation in the high-dose PEDV-inoculated gilt. PEDV RNA fecal titers were increased in contact exposed gilts after piglet PEDV challenge, but the low-dose PEDV and mock-inoculated gilts had the highest viral titers suggesting immune protection in the previously high-dose PEDV-inoculated gilt. (B) PEDV RNA fecal titers increased in piglets after PEDV challenge, but the piglets born to the low-dose PEDV and mock-inoculated gilts had higher viral titers suggesting lower immune protection. (C) The litter born to the high-dose PEDV inoculated gilt had delayed and lower PEDV RNA fecal titers throughout post-piglet challenge day (PCD) 8 and mean diarrhea scores <2 (defined as no watery diarrhea) throughout when compared with the low-dose PEDV and mock inoculated litters. After PEDV inoculation, piglets were monitored for clinical signs 2–3 times daily until necropsy. Diarrhea was assessed by scoring fecal consistency as follows: 0 = solid; 1 = pasty; 2 = semi-liquid; 3 = liquid. Scores of 2 or more are considered diarrheic. (A-B) PEDV RNA titers in fecal samples were determined by qRT-PCR. The detection limit of qRT-PCR was 4.8 log₁₀ GE/ml. (A-C) Each bar represents the mean ± SEM. Abbreviations: Post-inoculation day (PID), Piglet Challenge Day (PCD).

Fig. 3

A–B. Gilt geometric mean serum PEDV neutralization antibody titers. (A) Serum PEDV neutralization antibody titers were first detected in the high dose PEDV-inoculated gilt at mean gilt post-inoculation day (PID) 17 ± 2 [mean piglet challenge day (PCD) 2 ± 2] while low dose PEDV-inoculated gilt neutralizing antibody titers were delayed, being detectable at gilt mean PID 23 ± 2 (piglet PCD 3 ± 2). PEDV neutralizing antibody titers were not detected in the mock-inoculated gilt until gilt mean PID 39 ± 3 (piglet PCD 17 ± 2). (B) Milk PEDV neutralizing antibody titers were highest in colostrum and milk of the high dose PEDV-inoculated gilt. Serum and milk PEDV neutralizing antibody titers were delayed in the mock-inoculated gilts until mean PID 39 ± 3 (piglet PCD 17 ± 2) and mean PID 30 ± 2 (piglet PCD 10 ± 2), respectively. (Mean gilt post-partum day, PPD). See Fig. 2 for PID and PCD.