Augmentation of Immune Responses to HIV-1 and Simian Immunodeficiency Virus DNA Vaccines by IL-2/Ig Plasmid Administration in Rhesus Monkeys

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 8; pp. 4192 - 4197
• Main Authors: Barouch, Dan H., Craiu, Abie, Kuroda, Marcelo J., Schmitz, Jorn E., Zheng, Xin Xiao, Santra, Sampa, Frost, Julie D., Krivulka, Georgia R., Lifton, Michelle A., Crabbs, Carroll L., Heidecker, Gwendolyn, Perry, Helen C., Davies, Mary-Ellen, Xie, Hong, Nickerson, Christine E., Steenbeke, Tavis D., Lord, Carol I., Montefiori, David C., Strom, Terry B., Shiver, John W., Lewis, Mark G., Letvin, Norman L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 11-04-2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Amino Acid Sequence; Animals; Antibodies; Base Sequence; Biological Sciences; CD8 antigen; Cytokines; Deoxyribonucleic acid; DNA; DNA Primers; DNA vaccines; fusion protein; Gene Products, env - immunology; HIV; HIV 1; HIV Antibodies - biosynthesis; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; human immunodeficiency virus 1; Immunization; Immunoglobulin G - administration & dosage; Immunology; Interleukin-2 - administration & dosage; Lymphocytes; Macaca mulatta; Monkeys & apes; Plasmids; Plasmids - administration & dosage; Receptors, Interleukin-2 - immunology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Vaccination; Vaccines; Vaccines, DNA - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.050417697

The potential utility of plasmid DNA as an HIV-1 vaccination modality currently is an area of active investigation. However, recent studies have raised doubts as to whether plasmid DNA alone will elicit immune responses of sufficient magnitude to protect against pathogenic AIDS virus challenges. We therefore investigated whether DNA vaccine-elicited immune responses in rhesus monkeys could be augmented by using either an IL-2/Ig fusion protein or a plasmid expressing IL-2/Ig. Sixteen monkeys, divided into four experimental groups, were immunized with (i) sham plasmid, (ii) HIV-1 Env 89.6P and simian immunodeficiency virus mac239 Gag DNA vaccines alone, (iii) these DNA vaccines and IL-2/Ig protein, or (iv) these DNA vaccines and IL-2/Ig plasmid. The administration of both IL-2/Ig protein and IL-2/Ig plasmid induced a significant and sustained in vivo activation of peripheral T cells in the vaccinated monkeys. The monkeys that received IL-2/Ig plasmid generated 30-fold higher Env-specific antibody titers and 5-fold higher Gag-specific, tetramer-positive CD8+ T cell levels than the monkeys receiving the DNA vaccines alone. IL-2/Ig protein also augmented the vaccine-elicited immune responses, but less effectively than IL-2/Ig plasmid. Augmentation of the immune responses by IL-2/Ig was evident after the primary immunization and increased with subsequent boost immunizations. These results demonstrate that the administration of IL-2/Ig plasmid can substantially augment vaccine-elicited humoral and cellular immune responses in higher primates.