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The Journal of Immunology, 1998, 161: 1875-1882.
Copyright © 1998 by The American Association of Immunologists

Augmentation and Suppression of Immune Responses to an HIV-1 DNA Vaccine by Plasmid Cytokine/Ig Administration1

Dan H. Barouch*, Sampa Santra*, Tavis D. Steenbeke*, Xin X. Zheng{dagger}, Helen C. Perry{ddagger}, Mary-Ellen Davies{ddagger}, Daniel C. Freed{ddagger}, Abie Craiu*, Terry B. Strom{dagger}, John W. Shiver{ddagger} and Norman L. Letvin2,*

* Division of Viral Pathogenesis and {dagger} Division of Immunology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215; and {ddagger} Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486

The use of cytokines has shown promise as an approach for amplifying vaccine-elicited immune responses, but the application of these immunomodulatory molecules in this setting has not been systematically explored. In this report we investigate the use of protein- and plasmid-based cytokines to augment immune responses elicited by an HIV-1 gp120 plasmid DNA vaccine (pV1J-gp120) in mice. We demonstrate that immune responses elicited by pV1J-gp120 can be either augmented or suppressed by administration of plasmid cytokines. A dicistronic plasmid expressing both gp120 and IL-2 induced a surprisingly weaker gp120-specific immune response than did the monocistronic pV1J-gp120 plasmid. In contrast, systemic delivery of soluble IL-2/Ig fusion protein following pV1J-gp120 vaccination significantly amplified the gp120-specific immune response as measured by Ab, proliferative, and CTL levels. Administration of plasmid IL-2/Ig had different effects on the DNA vaccine-elicited immune response that depended on the temporal relationship between Ag and cytokine delivery. Injection of plasmid IL-2/Ig either before or coincident with pV1J-gp120 suppressed the gp120-specific immune response, whereas injection of plasmid IL-2/Ig after pV1J-gp120 amplified this immune response. To maximize immune responses elicited by a DNA vaccine, therefore, it appears that the immune system should first be primed with a specific Ag and then amplified with cytokines. The data also show that IL-2/Ig is more effective than native IL-2 as a DNA vaccine adjuvant.




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