Oral recombinant Lactobacillus vaccine targeting the intestinal microfold cells and dendritic cells for delivering the core neutralizing epitope of porcine epidemic diarrhea virus

Abstract

BackgroundPorcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) has led to serious economic losses to the swine industry worldwide. In this study, an oral recombinant Lactobacillus casei vaccine against PEDV infection targeting the intestinal microfold (M) cells and dendritic cells (DCs) for delivering the core neutralizing epitope (COE) of PEDV spike protein was developed with M cell-targeting peptide (Col) and dendritic cell-targeting peptide (DCpep). The immunogenicity of the orally administered recombinant strains was evaluated.ResultsAfter immunization, significantly higher levels of anti-PEDV specific IgG antibodies with PEDV neutralizing activity in the sera and mucosal sIgA antibodies in the tractus genitalis, intestinal mucus, and stools were detected in mice orally administered with the recombinant strain pPG-COE-Col-DCpep/L393, which expressed DCpep and Col targeting ligands fused with the PEDV COE antigen, compared to mice orally immunized with the recombinant strain pPG-COE/L393 without the DCpep and Col targeting ligands. Moreover, in response to restimulation with the PEDV COE antigen in vitro, a significant difference in splenocyte proliferation response and Th2-associated cytokine IL-4 level was observed in the group of mice orally immunized with pPG-COE-Col-DCpep/L393 (p < 0.05) compared to the groups of mice that received pPG-COE-Col/L393 and pPG-COE-DCpep/L393, respectively.ConclusionsThe intestinal M cells- and DCs-targeting oral delivery of genetically engineered Lactobacillus expressing the COE antigen of PEDV can efficiently induce anti-PEDV mucosal, humoral, and cellular immune responses via oral administration, suggesting a promising vaccine strategy against PEDV infection.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-0861-7) contains supplementary material, which is available to authorized users.

Immunogenicity and protective efficacy of orally administered recombinantLactobacillus plantarumexpressing VP2 protein against IBDV in chicken

“…Lactobacilli are attractive vaccine candidates because they have been successfully used as hosts for bacterial and viral antigen expression and can induce immune responses by oral administration (Maassen et al 1999;Grangette et al 2001;Reveneau et al 2002;Scheppler et al 2002;Ho et al 2005;Ma et al 2018). In addition, lactobacilli have demonstrated intrinsic adjuvant activity (Perdig on et al 2001;Ogawa et al 2005;Yu et al 2017).…”

Recombinant Lactobacillus casei Expressing Capsid Protein VP60 can Serve as Vaccine Against Rabbit Hemorrhagic Disease Virus in Rabbits

“…The sequences of the primers used for PCR amplification of VP60 were as follows: 5 -ATGGAGGGCAAAACCCGCACAGCGC-3 ; 5 -TCAGACATAAGAAAAGCCATTGGCT-3 . pPG-T7g10-PPT, constructed in our previous study [33], was used as a constitutive expression plasmid in this study; it encoded resistance to chloramphenicol (Cm) and contained an HCE promoter, T7g10 enhancer, PgsA anchor, and the rrnBT1T2 terminator. Plasmids pMD18-T simple-eGFP and pMD18-T simple-VP60 were constructed in our laboratory previously.…”

“…Currently, there is increasing interest in the development of L. casei oral vaccines, and this approach is significant for the effective induction of a mucosal immune response [30]. The results to date have been confirmed that the safety and the effectiveness of L. casei were used as the oral vaccine vehicle, which were extensively used in protecting individuals against a variety of pathogens [31][32][33][34][35][36][37].…”

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

“…PEDV strains cause porcine epidemic diarrhea (PED), characterized by vomiting, severe diarrhea, and dehydration in seronegative pigs at all ages, with high mortality in suckling pigs [3]. 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].…”