Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites

• Published in: The Journal of immunology (1950) Vol. 167; no. 3; pp. 1584 - 1591
• Main Authors: Horner, Anthony A, Datta, Sandip K, Takabayashi, Kenji, Belyakov, Igor M, Hayashi, Tomoko, Cinman, Nadya, Nguyen, Minh-Duc, Van Uden, John H, Berzofsky, Jay A, Richman, Douglas D, Raz, Eyal
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.08.2001
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - genetics; Administration, Intranasal; AIDS Vaccines - administration & dosage; AIDS Vaccines - chemical synthesis; AIDS Vaccines - genetics; AIDS Vaccines - immunology; Animals; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - chemical synthesis; Chemokines - metabolism; CpG Islands - immunology; Cytokines - metabolism; Cytotoxicity, Immunologic - genetics; Female; H-2 Antigens; HIV Envelope Protein gp120 - genetics; Human immunodeficiency virus; Immunity, Mucosal - genetics; Immunoglobulin A - biosynthesis; Immunoglobulin G - blood; Lymphocyte Activation - genetics; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides - administration & dosage; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - immunology; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Vaccines, DNA - administration & dosage; Vaccines, DNA - chemical synthesis; Vaccines, DNA - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.3.1584

Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.