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Journal of Virology, March 2001, p. 2130-2141, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2130-2141.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antigenicity and Immunogenicity of Novel Chimeric Hepatitis B Surface Antigen Particles with Exposed Hepatitis C Virus Epitopes†

Hans J. Netter,1,2,* Thomas B. Macnaughton,1,Dagger Wai-Ping Woo,1,2 Robert Tindle,1,2 and Eric J. Gowans1,2

Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Queensland 4029,1 and Clinical Medical Virology Research Centre, University of Queensland, St. Lucia, Queensland 4067,2 Australia

Received 25 August 2000/Accepted 5 December 2000

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.

* Corresponding author. Mailing address: Sir Albert Sakzewski Virus Research Centre, Herston Road, Herston, QLD 4029, Australia. Phone: 61-7-3636-7315. Fax: 61-7-3636-1401. E-mail: H.Netter{at}mailbox.uq.edu.au.

dagger Manuscript number 126 from SASVRC.

Dagger Present address: Howard Hughes Medical Institute and Department of Microbiology, University of Southern California School of Medicine, Los Angeles, CA 90033.

Journal of Virology, March 2001, p. 2130-2141, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2130-2141.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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