Vaccination of sows with a dendritic cell-targeted porcine epidemic diarrhea virus S1 protein-based candidate vaccine reduced viral shedding but exacerbated gross pathological lesions in suckling neonatal piglets

Abstract

Porcine epidemic diarrhea virus (PEDV) poses a serious threat to swine worldwide as evidenced by its recent introduction into the USA and the devastating economic impact it caused to the USA swine industry. Commercial vaccines against PEDV are available but their efficacies are inadequate. Therefore, vaccines with improved efficacy are needed to effectively control PEDV infections. We previously determined the immunogenicity of a novel dendritic cell (DC)-targeted PEDV S1 protein-based subunit vaccine in weaned piglets in which the PEDV antigen was targeted to DCs through a porcine Langerin-specific antibody. In this study, we evaluated the protective efficacy of this DC-targeting vaccine by immunizing sows at 5 and 2 weeks prior to farrowing and by challenging the 5-day-old piglets with PEDV. The results showed that immunization of sow with DC-targeted PEDV vaccine did not eliminate faecal virus shedding in piglets but significantly reduced faecal viral RNA levels in the early days after virus challenge. The vaccine also reduced the amount of PEDV antigen in intestinal tissues presented with intestinal villi regrowth. However, the DC-targeted vaccine neither mitigated PEDV clinical signs nor affected viral RNA loads in intestinal tissues of piglets. In the vaccinated sow, DC-targeted PEDV vaccine enhanced T helper 1-like cluster of differentiation (CD)4 T cell responses and induced IgG but not IgA-specific immune responses. The suckling piglets in the DC-targeted vaccine group showed increased gross pathological lesions in the small intestine. Results in this study provide insights into the effects of sow cellular immune responses to PEDV infection in suckling piglets.

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

“…However, it did not mitigate PEDV clinical signs or decrease viral RNA loads in the intestines of PEDV-challenged piglets [92]. Interestingly, piglets born to sows given the DC-targeted PEDV vaccine had enhanced gross pathological lesions in the small intestine compared to PEDV-challenged piglets born to unvaccinated mothers [92]. The authors hypothesized that the induction of CD4 + T cells with a Th1 phenotype may have stimulated complement-activating IgG2 virus-specific antibodies that passively transferred to piglets and increased inflammation in the gut.…”

“…In vaccinated sows, the DC-targeted PEDV vaccine enhanced IFN-γ-producing CD4 + T cells and induced IgG antibodies in colostrum/milk. However, it did not mitigate PEDV clinical signs or decrease viral RNA loads in the intestines of PEDV-challenged piglets [92]. Interestingly, piglets born to sows given the DC-targeted PEDV vaccine had enhanced gross pathological lesions in the small intestine compared to PEDV-challenged piglets born to unvaccinated mothers [92].…”

“…There is increasing interest in identifying vaccine adjuvants that effectively induce mucosal immune responses. As previously described, DC-targeted approaches have been developed to enhance mucosal delivery efficiency of PEDV antigens [69,92]. Recently, Wang and colleagues generated a recombinant Lacotobacillus (L393) to secrete a DC-targeted peptide conjugated to PEDV antigen.…”

“…These results are similar to those described earlier where sows vaccinated with a DC-targeted PEDV vaccine had increased IFN-γ-producing CD4 + T cells (Th1 phenotype). However, pPG-COE-DCpep/L393 will need to be evaluated in a pregnant and lactating sow model as increased IFN-γ-producing CD4 + T cells after DC-targeting PEDV vaccination of sows resulted in increased gross pathology in the intestines of PEDV-challenged piglets compared with piglets born from unvaccinated sows [92]. This demonstrates the importance of using sow models when developing PEDV vaccines aimed to protect suckling piglets.…”

Intramuscular Immunization with Chemokine-Adjuvanted Inactive Porcine Epidemic Diarrhea Virus Induces Substantial Protection in Pigs

“…Many attempts have been made to develop a safe and protective vaccine for controlling PED [4][5][6][7][8][9][10]. However, similar to studies on most enterotropic and mucosal transmissible viral diseases [11][12][13][14], using intramuscular (IM) administration of inactive or subunit vaccines combined with commercial adjuvants, such as multiple emulsions of water/oil/water or a B subunit of Escherichia coli heat-labile enterotoxin (LTB) induced production of systemic IgG and neutralizing antibodies but failed to elicit a mucosal IgA response and efficient protection [6,7,[15][16][17]. Furthermore, poor efficacies of currently commercialized vaccines have been reported [18][19][20].…”