Chitosan Nanoparticles Loaded with Truncated ORF2 Protein as an Oral Vaccine Candidate against Hepatitis E

Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to naïve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile.

Download Full-text

Hepatitis E vaccine candidate harboring a non-particulate immunogen of E2 fused with CRM197 fragment A

Antiviral Research ◽

10.1016/j.antiviral.2019.02.013 ◽

2019 ◽

Vol 164 ◽

pp. 154-161 ◽

Cited By ~ 1

Author(s):

Kaihang Wang ◽

Lizhi Zhou ◽

Xiao Zhang ◽

Cuiling Song ◽

Tingting Chen ◽

...

Keyword(s):

Vaccine Candidate ◽

Hepatitis E

Download Full-text

Truncated VP28 as oral vaccine candidate against WSSV infection in shrimp: An uptake and processing study in the midgut of Penaeus monodon

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2012.10.028 ◽

2013 ◽

Vol 34 (1) ◽

pp. 159-166 ◽

Cited By ~ 13

Author(s):

A. Kulkarni ◽

J.H.W.M. Rombout ◽

I.S.B. Singh ◽

N.S. Sudheer ◽

J.M. Vlak ◽

...

Keyword(s):

Vaccine Candidate ◽

Oral Vaccine ◽

Penaeus Monodon

Download Full-text

The Capsid (ORF2) Protein of Hepatitis E Virus in Feces Is C-Terminally Truncated

Pathogens ◽

10.3390/pathogens11010024 ◽

2021 ◽

Vol 11 (1) ◽

pp. 24

Author(s):

Takashi Nishiyama ◽

Koji Umezawa ◽

Kentaro Yamada ◽

Masaharu Takahashi ◽

Satoshi Kunita ◽

...

Keyword(s):

Amino Acids ◽

Cell Culture ◽

Structure Prediction ◽

Hepatitis E Virus ◽

Culture Media ◽

Molecular Size ◽

Hepatitis E ◽

Terminal Region ◽

Translation Product ◽

Orf2 Protein

The hepatitis E virus (HEV) is a causative agent of hepatitis E. HEV virions in circulating blood and culture media are quasi-enveloped, while those in feces are nonenveloped. The capsid (ORF2) protein associated with an enveloped HEV virion is reported to comprise the translation product of leucine 14/methionine 16 to 660 (C-terminal end). However, the nature of the ORF2 protein associated with fecal HEV remains unclear. In the present study, we compared the molecular size of the ORF2 protein among fecal HEV, cell-culture-generated HEV (HEVcc), and detergent-treated protease-digested HEVcc. The ORF2 proteins associated with fecal HEV were C-terminally truncated and showed the same size as those of the detergent-treated protease-digested HEVcc virions (60 kDa), in contrast to those of the HEVcc (68 kDa). The structure prediction of the ORF2 protein (in line with previous studies) demonstrated that the C-terminal region (54 amino acids) of an ORF2 protein is in flux, suggesting that proteases target this region. The nonenveloped nondigested HEV structure prediction indicates that the C-terminal region of the ORF2 protein moves to the surface of the virion and is unnecessary for HEV infection. Our findings clarify the maturation of nonenveloped HEV and will be useful for studies on the HEV lifecycle.

Download Full-text

Cytokine Profiles and Cell Proliferation Responses to Truncated ORF2 Protein in Iranian Patients Recovered from Hepatitis E Infection

Journal of Tropical Medicine ◽

10.1155/2015/523560 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Reza Taherkhani ◽

Fatemeh Farshadpour ◽

Manoochehr Makvandi ◽

Hamid Rajabi Memari ◽

Ali Reza Samarbafzadeh ◽

...

Keyword(s):

Cell Proliferation ◽

Immune Responses ◽

Mononuclear Cells ◽

Hepatitis E ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Orf2 Protein ◽

Cellular Immune ◽

Iranian Patients

Background.The aim of this study was to evaluatehepatitis E virus(HEV) specific cellular immune responses to truncated ORF2 protein in Iranian patients recovered from HEV infection. Information about HEV-specific immune responses could be useful in finding an effective way for development of HEV vaccine.Methods.A truncated form of HEV ORF2 protein containing amino acids 112-608 was used to stimulate peripheral blood mononuclear cells (PBMCs) separated from HEV-recovered and control groups. Finally, the levels of four cytokines, IFN-γELISPOT, and cell proliferative responses following stimulation with the truncated ORF2 protein were assessed in the both groups.Results.The truncated ORF2 protein was able to induce IFN-γELISPOT and cell proliferation responses and to produce significant amounts of IFN-γand IL-12 cytokines, but low amounts of IL-10 and IL-4 cytokinesin vitro. These responses were significantly higher in the recovered group compared to the control group. These results indicate the antigenic nature of the truncated ORF2 protein and production of T helper type 1 cytokines.Conclusion.The truncated ORF2 protein can effectively induce significant cellular immune responsesand can be introduced as a potential vaccine candidate. However, further studies are required to evaluate this proteinin vivo.

Download Full-text

Chimeric Recombinant Hepatitis E Virus-like Particles as an Oral Vaccine Vehicle Presenting Foreign Epitopes

Virology ◽

10.1006/viro.2001.1240 ◽

2002 ◽

Vol 293 (2) ◽

pp. 273-280 ◽

Cited By ~ 54

Author(s):

Masahiro Niikura ◽

Shiki Takamura ◽

Gisen Kim ◽

Satoru Kawai ◽

Masayuki Saijo ◽

...

Keyword(s):

Hepatitis E Virus ◽

Oral Vaccine ◽

Hepatitis E ◽

Recombinant Hepatitis ◽

Virus Like Particles

Download Full-text

Synthetic Peptides Containing Three Neutralizing Epitopes of Genotype 4 Swine Hepatitis E Virus ORF2 induced Protection against Swine HEV Infection in Rabbit

Vaccines ◽

10.3390/vaccines8020178 ◽

2020 ◽

Vol 8 (2) ◽

pp. 178

Author(s):

Yiyang Chen ◽

Tianxiang Chen ◽

Yuhang Luo ◽

Jie Fan ◽

Meimei Zhang ◽

...

Keyword(s):

Hepatitis E Virus ◽

Keyhole Limpet Hemocyanin ◽

Hepatitis E ◽

Genotype 4 ◽

Virus Shedding ◽

Fecal Shedding ◽

Orf2 Protein ◽

Swine Hepatitis ◽

Phosphate Buffered Saline ◽

Neutralizing Epitopes

Genotype 4 hepatitis E virus (HEV) is a zoonotic pathogen transmitted to humans through food and water. Previously, three genotype 4 swine HEV ORF2 peptides (407EPTV410, 410VKLYTS415, and 458PSRPF462) were identified as epitopes of virus-neutralizing monoclonal antibodies that partially blocked rabbit infection with swine HEV. Here, individual and tandem fused peptides were synthesized, conjugated to keyhole limpet hemocyanin (KLH), then evaluated for immunoprotection of rabbits against swine HEV infection. Forty New Zealand White rabbits were randomly assigned to eight groups; groups 1 thru 5 received three immunizations with EPTV-KLH, VKLYTS-KLH, PSRPF-KLH, EPTVKLYTS-KLH, or EPTVKLYTSPSRPF-KLH, respectively; group 6 received truncated swine HEV ORF2 protein (sp239), and group 7 received phosphate-buffered saline. After an intravenous swine HEV challenge, all group 7 rabbits exhibited viremia and fecal virus shedding by 2–4 weeks post challenge (wpc), seroconversion by 4–9 wpc, elevated alanine aminotransferase (ALT) at 2 wpc, and severe liver lymphocytic venous periphlebitis. Only 1–2 rabbits/group in groups 1–4 exhibited delayed viremia, fecal shedding, seroconversion, increased ALT levels, and slight liver lymphocytic venous periphlebitis; groups 5–6 showed no pathogenic effects. Collectively, these results demonstrate that immunization with a polypeptide containing three genotype 4 HEV ORF2 neutralizing epitopes completely protected rabbits against swine HEV infection.

Download Full-text