Hepatitis E virus vaccine and method

Abstract

Antigen and antibody vaccine composition effective in preventing hepatitis E virus (HEV) infection are disclosed. The antigen composition includes a peptide corresponding to a carboxyl terminal end region of the capsid protein encoded by the second open reading frame 2 of the HEV genome. The composition is effective in preventing HEV infection after vaccination. The antibody composition contains an antibody effective to block HEV infection of human primary hepatocytes in culture.

Description

[0001] This application is a continuation-in-part of U.S. application Ser. No. 07 / 882,335, filed Jan. 17, 1992, which is a continuation-in-part of application Ser. No. 07 / 505,888, filed Apr. 5, 1990, which is a continuation-in-part of U.S. application Ser. No. 420,921, filed Oct. 13, 1989, which is a continuation-in-part of U.S. application Ser. No. 367,486, filed Jun. 16, 1989, which is a continuation-in-part of U.S. Application Serial No. 336,672, filed Apr. 11, 1989, which is a continuation-in-part of U.S. application Ser. No. 208,997, filed Jun. 17, 1988, all of which are herein incorporated by reference.1. FIELD OF INVENTION[0002] This invention relates to antigen and antibody vaccine compositions related to enterically transmitted nonA / nonB hepatitis viral agent, also referred to herein as hepatitis E virus (HEV), and to vaccine methods.2. REFERENCES[0003] Arankalle, V. A., et al., The Lancet, 550 (Mar. 12, 1988).[0004] Bradley, D. W., et al., J Gen. Virol., 69:1 (1988).[0005]...

AI Technical Summary

Benefits of technology

[0104] The recombinant or intact HEV capsid or capsid fragment peptides (HEV capsid antigens) described above are incorporated into a vaccine composition, according to known procedures, to enhance the antigenicity of the injected antigens.

[0114] At this stage, two of the four experimental animals received a third inoculation of non-adjuvanted, insoluble trpE-C2 peptide antigen. Four weeks later, these animals showed anti-HEV antibodies, as evidenced by Western blots. These results suggest that the trpE-C2 antigen may be more effective when administered in the absence of alum, possibly because of alum-denaturation of the antigen during the alum co-precipitation procedure.

[0118] FIG. 3A shows the change in liver ALT levels following infection with Mexico-strain HEV virus, in one of the animals which received a third dose of trpE-C2. Again, there was no evidence of elevated ALT levels out to day 32 (The animal died of unrelated causes at day 32). The liver biopsy samples also showed minimal evidence of HEV antigen. This result demonstrates that an antigen vaccine directed against one HEV strain can provide protective immunity against other HEV strains.

[0123] The antibodies in the composition are preferably immunoreactive with a peptide containing one of the sequences: Sequence ID No. 13; Sequence ID No. 14, and internally consistent variations between Sequence ID Nos. 13 and 14. As will be seen below, antibodies prepared against the 406.3-2 antigen (M) are effective to block HEV infection in human primary hepatocytes.

[0132] The primary hepatocytes were prepared and cultured according to published procedures and as detailed in Example 1. The unique culture conditions allow for long-term cell growth in culture without loss of specialized hepatocyte function, as evidenced by the cells' continued ability to make and secrete liver-specific proteins, such as serum albumin, up to several months after initial culturing, as described in Example 1.

Problems solved by technology

The course of HEV is generally uneventful in healthy individuals, and the vast majority of those infected recover without the chronic sequelae seen with HCV.

Images