Immunogenicity of candidate hepatitis E virus DNA vaccine expressing complete and truncated ORF2 in mice

Deshmukh, Tejaswini M.; Lole, Kavita S.; Tripathy, Anuradha S.; Arankalle, Vidya A.

doi:10.1016/j.vaccine.2007.03.040

Cited by 44 publications

(27 citation statements)

References 35 publications

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“…With the expression of the capsid protein (rORF2p) in the baculovirus expression system [17] , a preliminary study was conducted during [2003][2004][2005][2006]. Since all the FHF patients were admitted to a single unit of a medical college hospital, the treatment protocol was not responsible for differential outcome of FHF.…”

Section: Discussionmentioning

confidence: 99%

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Viral Load, Antibody Titers and Recombinant Open Reading Frame 2 Protein-Induced Th1/Th2 Cytokines and Cellular Immune Responses in Self-Limiting and Fulminant Hepatitis E

et al. 2009

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Objectives: Hepatitis E virus (HEV) is the predominant cause of water-borne epidemics, sporadic acute viral hepatitis (AVH) in adults and fulminant hepatic failure (FHF) among pregnant women and other adults in India. This preliminary study was designed to examine the association of viral load and certain host immune responses with uneventful recovery or progression to FHF. Methods: Viral load, anti-HEV antibody titers, rORF2p-induced Th1/Th2 cytokines levels and cellular immune responses were assessed in 47 patients with self-limiting hepatitis E and 14 FHF-E cases. The controls included 16 anti-HEV-IgM and IgG-negative healthy individuals. Results: In AVH category, the viral load was 2.4 × 10⁴ ± 1.92 × 10⁴ copies/ml while except for one, all FHF patients were negative for HEV RNA; anti-HEV-IgM and IgG titers were higher in the FHF group. Lymphocyte proliferative response to rORF2p was comparable in both groups. As compared to AVH, significantly higher levels of both Th1 (IFN-γ, IL-2 and TNF-α) and Th2 (IL-10) cytokines were recorded in FHF patients. Analysis of sequential samples differentiated FHF recovered and fatal patients with respect to IFN-γ and IL-12. Conclusion: The results document increased Th1/Th2 responses and anti-HEV titers in FHF patients that warrant in-depth immunological studies.

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Section: Discussionmentioning

confidence: 99%

“…10 6 cells/well were set up in 6-well plate (Nunc, Denmark). Cells were stimulated with HPLC purified rORF2p from genotype-1 HEV [17] . Supernatants from cultured cells were harvested after 72 h and stored at -70 °.…”

Section: Stimulation Of Pbmcs and Cytokine Assaymentioning

confidence: 99%

Viral Load, Antibody Titers and Recombinant Open Reading Frame 2 Protein-Induced Th1/Th2 Cytokines and Cellular Immune Responses in Self-Limiting and Fulminant Hepatitis E

et al. 2009

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“…HEV regularly causes epidemics in many tropical and subtropical countries. In India, 101 outbreaks were confirmed by serological analysis in the state of Maharashtra in the last 5 years (6), and the lifetime risk of HEV infection exceeds 60% (28). Sporadic cases have also been reported in regions where HEV is endemic, as well as in areas where it is not endemic.…”

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confidence: 99%

Spatial Configuration of Hepatitis E Virus Antigenic Domain

Wang

et al. 2011

J Virol

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Hepatitis E virus (HEV) is a human pathogen that causes acute hepatitis. When an HEV capsid protein containing a 52-amino-acid deletion at the C terminus and a 111-amino-acid deletion at the N terminus is expressed in insect cells, the recombinant HEV capsid protein can self-assemble into a T‫1؍‬ virus-like particle (VLP) that retains the antigenicity of the native HEV virion. In this study, we used cryoelectron microscopy and image reconstruction to show that anti-HEV monoclonal antibodies bind to the protruding domain of the capsid protein at the lateral side of the spikes. Molecular docking of the HEV VLP crystal structure revealed that Fab224 covered three surface loops of the recombinant truncated second open reading frame (ORF2) protein (PORF2) at the top part of the spike. We also determined the structure of a chimeric HEV VLP and located the inserted B-cell tag, an epitope of 11 amino acids coupled to the C-terminal end of the recombinant ORF2 protein. The binding site of Fab224 appeared to be distinct from the location of the inserted B-cell tag, suggesting that the chimeric VLP could elicit immunity against both HEV and an inserted foreign epitope. Therefore, the T‫1؍‬ HEV VLP is a novel delivery system for displaying foreign epitopes at the VLP surface in order to induce antibodies against both HEV and the inserted epitope.Hepatitis E virus (HEV) is a causative agent of acute hepatitis in humans and is primarily transmitted via the fecal-oral route. HEV is thus resistant to the low pH and digestive enzymes associated with the stomach and gastrointestinal tract. HEV regularly causes epidemics in many tropical and subtropical countries. In India, 101 outbreaks were confirmed by serological analysis in the state of Maharashtra in the last 5 years (6), and the lifetime risk of HEV infection exceeds 60% (28). Sporadic cases have also been reported in regions where HEV is endemic, as well as in areas where it is not endemic. Although some of these cases were associated with travel, many cases involved patients without a history of travel to regions where HEV is endemic. Accumulating evidence suggests that sporadic infection occurs through a zoonotic route and is not limited to developing countries. Seroprevalence suggests hepatitis E infection may also be prevalent in high-income countries (21), such as the United States (17), the United Kingdom (3), and Japan (18). The overall mortality rate of HEV infection during an outbreak generally ranges from 1 to 15%, and the highest mortality occurs in pregnant women, with fatality rates of up to 30% (19).The HEV virion is composed of a 7.2-kb single-stranded RNA molecule and a 32-to 34-nm icosahedral capsid. The HEV genome contains three open reading frames (ORFs).The capsid protein, encoded by the second open reading frame (ORF2), located at the 3Ј terminus of the genome, comprises 660 amino acids and is responsible for most capsid-related functions, such as assembly, host interaction, and immunogenicity. Recombinant ORF2 proteins can induce antibodies that block...

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“…The vaccine was also found to be immunogenic and resulted in vaccinated persons in a high level of protection against infection with HEV-1 prevalent in Nepal [213]. Additional experimental vaccines based on recombinant HEV proteins or HEV DNA coding for ORF2 are being investigated in various model systems for their immunogenicity and cross-reactivity [24,214,215,216]. Up to now no licenced vaccines are available in Europe.…”

Section: Recipientsmentioning

confidence: 99%