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Journal of Virology, July 2002, p. 6652-6659, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6652-6659.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of DNA-Raised Immune Responses by Cotransfected Interferon Regulatory Factors

Shin Sasaki,1,{dagger} Rama Rao Amara,1 Wen-Shuz Yeow,2 Paula M. Pitha,2 and Harriet L. Robinson1*

Division of Microbiology and Immunology, Yerkes National Primate Research Center and Vaccine Research Center of Emory University School of Medicine, Atlanta, Georgia 30329,1 Oncology Center, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 212312

Received 10 December 2001/ Accepted 3 April 2002

Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold. Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased towards type 1 immune responses and the production of gamma interferon. Following gene gun bombardments of DNA, both were biased towards type 2 immune responses and the production of interleukin-4. The biases of the T-cell responses towards type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.

* Corresponding author. Mailing address: Yerkes National Primate Research Center, 954 Gatewood Rd. NE, Atlanta, GA 30329. Phone: (404) 727-7217. Fax: (404) 727-7768. E-mail: hrobins{at}rmy.emory.edu.

{dagger} Present address: National Institute of Infectious Diseases, Tokyo, Japan.

Journal of Virology, July 2002, p. 6652-6659, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6652-6659.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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