Oral Vaccination with Hepatitis E Virus Capsid Protein and Immunobiotic Bacterium-Like Particles Induce Intestinal and Systemic Immunity in Mice

ARCE, L. P.; RAYA TONETTI, M. F.; RAIMONDO, M. P.; MÜLLER, M. F.; SALVA, S.; ÁLVAREZ, S.; BAIKER, A.; VILLENA, J.; VIZOSO PINTO, M. G.

Probiotics and Antimicrobial Proteins

Springer

Año: 2019

1867-1306

The hepatitis E virus (HEV) genotype 3 (GT3) is an emergent pathogen in industrialized countries. It is transmitted zoonotically andmay lead to chronic hepatitis in immunocompromised individuals.We evaluated if the major antigen of HEV, the capsid protein, canbe used in combination with immunobiotic bacterium-like particles (IBLP) for oral vaccination in a mouse model.We have clonedand expressed the RGS-His5-tagged HEV GT3 capsid protein (ORF2) in E. coli and purified it by NiNTA. IBLP were obtainedfrom two immunobiotic Lactobacillus rhamnosus strains acid- and heat-treated. ORF2 and the IBLP were orally administered toBalb/c mice. After three oral immunizations (14-day intervals), blood, intestinal fluid, Peyer´s patches, and spleen samples weredrawn. IgA- and IgG-specific antibodies were determined by ELISA. Mononuclear cell populations from Peyer?s patches andspleen were analyzed by flow cytometry, and the cytokine profiles were determined by ELISA to study cellular immunity. Orallyadministered recombinant ORF2 and IBLP from two L. rhamnosus strains (CRL1505 and IBL027) induced both antigen-specifichumoral and cellular immune responses in mice. IBLP027 was more effective in inducing specific secretory IgA in the gut. IFN-γ,TNF-α, and IL-4 were produced by Peyer?s plaques lymphocytes stimulated with ORF2 ex vivo suggesting a mixed Th1/Th2-typeadaptive immune response in immunized mice. Oral vaccines are not invasive, do not need to be administered by specializedpersonal, and elicit both systemic and local immune responses at the port of entry. Here, we present an experimental oral vaccine forHEV GT3, which could be further developed for human and/or veterinary use.