Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites.
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.
Horner
A A
AA
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Datta
S K
SK
Takabayashi
K
K
Belyakov
I M
IM
Hayashi
T
T
Cinman
N
N
Nguyen
M D
MD
Van Uden
J H
JH
Berzofsky
J A
JA
Richman
D D
DD
Raz
E
E
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D018925:Chemokines / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D006183:H-2 Antigens; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D018928:Immunity, Mucosal / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D019444:Vaccines, DNA