Efficacy of orally administered porcine epidemic diarrhea vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres and RANKL-secreting L. lactis

Abstract

Here, we examined the efficacy of are combinant subunit antigen-based oral vaccine for preventing porcine epidemic diarrhea virus (PEDV). First, we generated a soluble recombinant partial spike S1 protein (aP2) from PEDV in E. coli and then evaluated the utility of aP2 subunit vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres (HPMCP) and RANKL-secreting L. lactis (LLRANKL) as a candidate oral vaccine in pregnant sows. Pregnant sows were vaccinated twice (with a 2 week interval between doses) at 4 weeks before farrowing. Titers of virus-specific IgA antibodies in colostrum, and neutralizing antibodies in serum, of sows vaccinated with HPMCP (aP2) plus LL RANKL increased significantly at 4 weeks post-first vaccination. Furthermore, the survival rate of newborn suckling piglets delivered by sows vaccinated with HPMCP (aP2) plus LL RANKL was similar to that of piglets delivered by sows vaccinated with a commercial killed porcine epidemic diarrhea virus (PED) vaccine. The South Korean government promotes a PED vaccine program (live-killed-killed) to increase the titers of IgA and IgG antibodies in pregnant sows and prevent PEDV. The oral vaccine strategy described herein, which is based on a safe and efficient recombinant subunit antigen, is an alternative PED vaccination strategy that could replace the traditional strategy, which relies on attenuated live oral vaccines or artificial infection with virulent PEDV.

Efficacy of Needle-Less Intradermal Vaccination against Porcine Epidemic Diarrhea Virus

“…In addition, a significant positive effect on average daily weight gain (between 44 and 59 g/day) in the finishing phase was observed from pigs administered with the PCV2 vaccine via the ID route [4]. The survival rate after challenge of newborn suckling piglets delivered by sows vaccinated with ID PED vaccine in this study was similar to that of piglets delivered by sows vaccinated with PED aP2 subunit vaccine (loaded hydroxypropyl methylcellulose phthalate microspheres plus RANKL-secreting L. lactis) [33].…”

Oral delivery of maize-produced porcine epidemic diarrhea virus spike protein elicits neutralizing antibodies in pigs

“…In the study by Makadiya et al maximum titers of approximately 90 (unconverted titer) are reported after injection of purified recombinant protein (Makadiya et al 2016). In a more recent report (Choe et al 2020), a similar neutralizing antibody titer of 7-8 on a log 2 scale was obtained on oral immunization with S1-containing microspheres. The work presented here indicates that the orally-delivered S1 produced in maize can elicit a response similar to other subunit vaccine delivery systems.…”

Porcine epidemic diarrhea virus: Molecular mechanisms of attenuation and vaccines

“…At present, two strategies have been used to induce mucosal immunity. The first one involves applying suitable carriers for delivering vaccines by mucosal routes; a whole PEDV attenuated strain entrapped in the enteric material hydroxypropyl methyl cellulose phthalate (HPMCP) successfully induced both mucosal immunity and systemic immunity after oral immunization in weaned piglets [ 181 , 182 ]. PEDV killed vaccine antigens (KAg) entrapped in PLGA particles was delivered intranasally to sows at 28 and 14 days prior to farrowing.…”