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Journal of Virology, October 2004, p. 11321-11326, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11321-11326.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Protective Efficacy of a DNA Influenza Virus Vaccine Is Markedly Increased by the Coadministration of a Schiff Base-Forming Drug

Jehad Charo,1,{dagger}* Jan Alvar Lindencrona,1,{dagger} Lena-Maria Carlson,1 Jorma Hinkula,2 and Rolf Kiessling1

Department of Oncology-Pathology,1 Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden2

Received 6 February 2004/ Accepted 9 June 2004

Effective vaccination against heterologous influenza virus infection remains elusive. Immunization with plasmid DNA (pDNA) expressing conserved genes from influenza virus is a promising approach to achieve cross-variant protection. However, despite having been described for more than a decade, pDNA vaccination still requires further optimization to be applied clinically as a standard vaccination approach. We have recently described a simple and efficient approach to enhance pDNA immunization, based on the use of tucaresol, a Schiff base-forming drug. In this report we have tested the ability of this drug to increase the protection conferred by pDNA vaccination against influenza virus infection. Our results demonstrate that a significant protection was achieved in two strains of mice by using the combination of pDNA and tucaresol. This protection was associated with an elevated humoral and cellular response and a switch in the type of the T helper cell (Th) immune response from type 2 to type 1. This vaccine combination represents a promising strategy for designing a clinical study for the protection from influenza and similar infections.

* Corresponding author. Mailing address: Cancer Center Karolinska (CCK), Karolinska Hospital, R8:01, S-17176 Stockholm, Sweden. Phone: 468-517-76876. Fax: 468-309195. E-mail: Jehad.Charo{at}mtc.ki.se.

{dagger} J.C. and J.A.L. have contributed equally to this study.

Journal of Virology, October 2004, p. 11321-11326, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11321-11326.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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