Enhancement of Hepatitis E Virus DNA Vaccine Immunity by Beclin-1- Mediated Autophagy

Abstract

Background: The Hepatitis E virus (HEV) infection is a serious public health problem, with a mortality rate of approximately 20-25% among pregnant women. DNA vaccination was reported to induce humoral and cellular immune responses in murine models; however, a major problem of the strategy is its limited potency. Methods: In this study, we have investigated whether Beclin1, as an autophagy-inducing based plasmid, can serve as an immunostimulatory agent and promote the HEV specific protective immunity of naked DNA vaccine encoding truncated ORF-2 (HEV239). Plasmids encoding HEV239 with or without Beclin1 were used for the BALB/c mice immunization. Results:The results demonstrated a significant increase microtubule-associated protein light chain-3 II (LC3 II) as a marker of autophagy in the HEK293 cell, which were transfected by pVITRO-Beclin1 plasmid. The immunological effects of adding Beclin1 to HEV239 ORF-2 DNA vaccines were associated with the induction of the antigen-specific lymphocyte proliferation and the Th1-type cytokine (gamma-interferon (IFN-γ)), while there were no differences in IL-4 levels between the groups. Examination of humoral immune responses in vaccinated mice represented that immunization with pVITRO-HEV239-Beclin1 notably increased serum level of IgG2a and total IgG against HEV in comparison to the HEV239 plasmid alone. Conclusions:The strong Th1 immune response induced by the Beclin1 suggest that induction of autophagy can be an efficient approach to enhance the immunogenicity of DNA vaccine. This promising procedure could be further exploited as a potential therapeutic vaccine candidate in future studies.

Antitumor Effects of HPV DNA Vaccine Adjuvanted with Beclin-1 as an Autophagy Inducer in a Mice Model

“…Khateri et al [ 13 ] have reported that mice immunized with hepatitis E virus vaccine formulated with Beclin-1 display a humoral and cellular response. This observation has also been confirmed by Naziri et al [ 14 ] . It has been reported that autophagy causes additional processing of the antigen, probably due to the engulfment of the antigen by autophagosomes and delivery to lysosomes for MHC-restricted antigen presentation [ 33 ] .…”

“…Using adjuvants to induce authophagy is a promising strategy for enhancing immune responses [ 13 , 14 ] . Autophagy is an extremely preserved and continuous biological proccess that can lead to the surrounding of cytoplasmic contents in a cup-shaped double-membrane or multi-membrane-bound structures known as an autophagosome [ 15 ] .…”

Design and construction of Beclin1-expressing plasmid as an autophagy inducing system: a novel strategy for enhancing the potency of DNA vaccines

“…Interestingly, most of these viruses restrain autophagosome generation or maturation via binding to Beclin1 [9]. Limited immunogenicity of DNA vaccines is the main obstacle for DNA vaccines; however, several novel and promising approaches have been suggested to enhance the potency of such vaccines [10][11][12][13]. Based on the ability of autophagy in the augmentation of the immune responses, here we evaluated the induction of autophagy through constructing a plasmid expressing Beclin1 in an in vitro model.…”

Autophagy: The multi‐purpose bridge in viral infections and host cells

“…Our team formulated Beclin‐1, an autophagy initiator, as an adjuvant with an HEV candidate DNA vaccine in a mouse model. The immunized mice induced robust immune response but have not significant effect on HEV protein candidate vaccine . The role of autophagy in apoptosis of uninfected bystander cells, adaptive immunity by viral processing and MHC‐antigen presentation, and in innate immunity by affecting pathogen sensing opens novel approaches for an HIV‐1 vaccine and combination treatment strategies .…”