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INDUCTION OF BIVALENT IMMUNE RESPONSES BY EXPRESSION OF DENGUE VIRUS TYPE 1 AND TYPE 2 ANTIGENS FROM A SINGLE COMPLEX ADENOVIRAL VECTOR

There are approximately 100 million new cases of dengue (DEN) virus infection each year. Infection can result in illness ranging from a mild fever to hemorrhaging, shock, or even death. There are four serotypes of dengue virus (DEN1–4), and immunity to one serotype does not cross protect from infection with other serotypes. Currently there are no approved vaccines for dengue fever. In this report, we describe the construction of a bivalent dengue virus vaccine using a complex recombinant adenovirus approach to express multiple genes of DEN1 and DEN2 serotypes. In vaccinated mice, this vector induced humoral immune responses against all four dengue serotypes as measured by enzyme-linked immunosorbent assay. However, the neutralizing antibody responses were specific for DEN1 and DEN2 serotypes. Expansion of this vaccine development platform towards the DEN3 and DEN4 serotypes can lead towards the development of an adenovirus-based tetravalent dengue vaccine.

Received April 26, 2006. Accepted for publication November 18, 2006.

Acknowledgments: We thank Dr. Barry Falgout for the dengue virus isolates that aided in our research and the U.S. Army Research Institute for Infectious Diseases for the dengue hybridoma cells lines. We also thank Andres Ayuso, Benjamin Swain, and Kevin Moore for their dedicated efforts in assisting with this study.

Financial support: This study was supported by a grant from the Department of Health and Human Services (award no. R43A153049-01).

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government.

^* Address correspondence to John Y. Dong, Division of Biodefense Vaccines, GenPhar Incorporated, 871 Lowcountry Boulevard, Mount Pleasant, SC 29464. E-mail: dongj{at}genphar.com

Authors’ addresses: Nicholas U. Raja, David H. Holman, Danher Wang, Laure Y. Juompan, Stephen B. Deitz, Min Luo, and Jianghui Zhang, Division of Biodefense Vaccines, GenPhar Incorporated, 871 Lowcountry Boulevard, Mount Pleasant, SC 29464, Telephone: 843-884-0120, Fax: 843-884-0601. Kanakatte Raviprakash and Kevin R. Porter, Naval Medical Research Center, 503 Robert Grant Avenue, Building 503, Room 3A14A, Silver Spring, MD 20910-7500, Telephone: 301-319-7454. John Y. Dong, Division of Biodefense Vaccines, GenPhar Incorporated, 871 Lowcountry Boulevard, Mount Pleasant, SC 29464, Telephone: 843-884-0120, Fax: 843-884-0601, E-mail: dongj{at}genphar.com and Medical University of South Carolina, 173 Ashley Avenue, BSB-201, Charleston, SC 29403, Telephone: 843-792-1018, Fax: 843-792-2464.

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