Augmentation and suppression of immune responses to an HIV-1 DNA vaccine by plasmid cytokine/Ig administration

Dan H. Barouch, Sampa Santra, Tavis D. Steenbeke, Xin X. Zheng, Helen C. Perry, Mary Ellen Davies, Daniel C. Freed, Abie Craiu, Terry B. Strom, John W. Shiver, Norman L. Letvin

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137 Scopus citations

Abstract

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 pVIJ-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.

Original languageEnglish
Pages (from-to)1875-1882
Number of pages8
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - 15 Aug 1998
Externally publishedYes

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