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Journal of Virology, November 2005, p. 13656-13666, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13656-13666.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combinatorial Approach to Hepadnavirus-Like Particle Vaccine Design

Jean-Noel Billaud,1 Darrell Peterson,2 Margaret Barr,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 Milich1*

Vaccine Research Institute of San Diego, California 92109,1 Department of Biochemistry and Molecular Biophysics, Commonwealth University, Richmond, Virginia,2 College of Veterinary Medicine, Western University, Pomona, California 91766,3 Division of Clinical Virology, Karolinska University Hospital, Karolinska Institute, Huddinge, Sweden4

Received 25 May 2005/ Accepted 10 August 2005

The particulate hepatitis core protein (HBcAg) represents an efficient carrier platform with many of the characteristics uniquely required for the delivery of weak immunogens to the immune system. Although the HBcAg is highly immunogenic, the existing HBcAg-based platform technology has a number of theoretical and practical limitations, most notably the "preexisting immunity" and "assembly" problems. To address the assembly problem, we have developed the core protein from the woodchuck hepadnavirus (WHcAg) as a new particulate carrier platform system. WHcAg appears to tolerate insertions of foreign epitopes at a greater number of positions than HBcAg. For example, both within the external loop region and outside the loop region a total of 17 insertion sites were identified on WHcAg. Importantly, the identification of an expanded number of insertion sites was dependent on additional modifications to the C terminus that appear to stabilize the various internal insertions. Indeed, 21 separate C-terminal modifications have been generated that can be used in combination with the 17 insertion sites to ensure efficient hybrid WHcAg particle assembly. This combinatorial technology is also dependent on the sequence of the heterologous insert. Therefore, the three variables of insert position, C terminus, and epitope sequence are relevant in the design of hybrid WHcAg particles for vaccine purposes.

* 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.

Journal of Virology, November 2005, p. 13656-13666, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13656-13666.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lee, B. O., Tucker, A., Frelin, L., Sallberg, M., Jones, J., Peters, C., Hughes, J., Whitacre, D., Darsow, B., Peterson, D. L., Milich, D. R. (2009). Interaction of the Hepatitis B Core Antigen and the Innate Immune System. J. Immunol. 182: 6670-6681 [Abstract] [Full Text]  
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  • Billaud, J.-N., Peterson, D., Schodel, F., Chen, A., Sallberg, M., Garduno, F., Goldstein, P., McDowell, W., Hughes, J., Jones, J., Milich, D. (2005). Comparative Antigenicity and Immunogenicity of Hepadnavirus Core Proteins. J. Virol. 79: 13641-13655 [Abstract] [Full Text]  


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