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CpG‐C ISS‐ODN activation of blood‐derived B cells from healthy and chronic immunodeficiency virus‐infected macaques
Author(s) -
Teleshova N.,
Kenney J.,
Williams V.,
Van Nest G.,
Marshall J.,
Lifson J. D.,
Sivin I.,
Dufour J.,
Bohm R.,
Gettie A.,
Pope M.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0205084
Subject(s) - biology , simian immunodeficiency virus , chemokine , cxcl16 , cd40 , virology , immunology , cd80 , cd86 , cxcl13 , cytokine , macaque , b cell , cxcl10 , immune system , t cell , chemokine receptor , cytotoxic t cell , antibody , in vitro , paleontology , biochemistry
Cytosine‐phosphate‐guanine class C (CpG‐C) immunostimulatory sequence oligodeoxynucleotides (ISS‐ODNs) activate human B cells and dendritic cells (DCs), properties that suggest potential use as a novel adjuvant to enhance vaccine efficacy. After demonstrating that the CpG‐C ISS‐ODN C274 activates macaque DCs, we examined in vitro activation of macaque B cells by C274 as a prelude to evaluation of this molecule as an adjuvant in the testing of candidate human immunodeficiency virus vaccines in the rhesus macaque‐simian immunodeficiency virus (SIV) model. C274 induced macaque CD20 + B cells to proliferate more strongly than CD40 ligand or CpG‐B ISS‐ODN. C274 enhanced B cell survival; increased viability was most evident after 3–7 days of culture. Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week. C274‐stimulated, B cell‐enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus‐infected monkeys secreted several cytokines [e.g., interleukin (IL)‐3, IL‐6, IL‐12, interferon‐α] and chemokines [e.g., monocyte chemoattractant protein‐1/CC chemokine ligand 2 (CCL2), macrophage‐inflammatory protein‐1α/CCL3, IL‐8/CXC chemokine ligand 8]. In comparison, exposure of macaque B cells to SIV had minimal impact on surface phenotype, despite inducing cytokine and chemokine production in cells from infected and uninfected animals. These observations emphasize the need to identify strategies to optimally boost immune function, as immunodeficiency viruses themselves only partially activate B cells and DCs. The ability of C274 to stimulate B cells and DCs in healthy and infected monkeys suggests its possible use as a broad‐acting adjuvant to be applied in the rhesus macaque model for the development of preventative and therapeutic vaccines.