The Interplay of antigen and antibody in HEV infection

Although infection with the Hepatitis E Virus (HEV) is the most common cause of acute viral hepatitis worldwide, the serological response in HEV infected patients is not yet fully understood. Interestingly, immunocompromised individuals are often unable to clear the virus and develop chronic infection. During HEV infection, high amounts of glycosylated and non-infectious dimers of HEV’s capsid protein (pORF2) are secreted. These dimers can be found in the serum even after clearance of the virus as determined by undetected HEV-RNA in stool and serum. We hypothesize that among other mechanisms, the lack of glycan sensitive antibodies not captured by these glycosylated forms of the capsid protein, contributes to a chronic disease course. We therefore aim to further investigate the interplay of antigen secretion and antibody detection over the course of HEV infections.

To this end, we established two enzyme linked immunosorbent assays (ELISA). First, we established an ELISA that detects anti-pORF-2-IgG in patients. To reach a higher specificity, we only use the protruding domain of pORF2 for detection, which is the target of neutralizing antibodies. Secondly, we established a sandwich-ELISA detecting pORF2 in patient sera. Importantly, this ELISA can differentiate between only non-glycosylated, infectious pORF2 and total pORF2 present. Ultimately, we want to correlate the course of antigen positivity and IgG response in different patients with different clinical courses of HEV infection.

This will lead to a better understanding of the interplay of antigen and antibody response in HEV infections and might identify determinants for the clinical outcome.

 

MissingLinkText

Publication History

Article published online:
18 January 2023