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Journal of Virology, November 2005, p. 13641-13655, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13641-13655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Comparative Antigenicity and Immunogenicity of Hepadnavirus Core Proteins

Jean-Noel Billaud,¹ Darrell Peterson,² Florian Schödel,³ Antony Chen,^1,4 Matti Sallberg,⁴ Fermin Garduno,¹ Phillip Goldstein,¹ Wendy McDowell,¹ Janice Hughes,¹ Joyce Jones,¹ and David Milich^1*

Vaccine Research Institute of San Diego, San Diego, California 92109,¹ Department of Biochemistry and Molecular Biophysics, Commonwealth University, Richmond, Virginia,² Merck Research Laboratories, West Point, Pennsylvania,³ Division of Clinical Virology, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden⁴

Received 25 May 2005/ Accepted 10 August 2005

The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate "eAgs" do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4⁺ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the "preexisting" immunity problem that is inherent in the use of HBcAg for human vaccine development.

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* Corresponding author. Mailing address: Vaccine Research Institute of San Diego, 3030 Bunker Hill Street, Suite 300, San Diego, CA 92109. Phone: (858) 581-3960. Fax: (858) 581-3970. E-mail: dmilich{at}vrisd.org.

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Journal of Virology, November 2005, p. 13641-13655, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13641-13655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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