{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T12:49:18Z","timestamp":1759063758961},"reference-count":54,"publisher":"American Society for Microbiology","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Most DNA-encoded adjuvants enhance immune responses to DNA vaccines in small animals but are less effective in primates. Here, we characterize the adjuvant activity of the catalytic A1 domain of cholera toxin (CTA1) for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) antigens in mice and macaques delivered by GeneGun. The inclusion of CTA1 with SIVmac239 Gag dramatically enhanced anti-Gag antibody responses in mice. The adjuvant effects of CTA1 for the secreted antigen HIV gp120 were much less pronounced than those for Gag, as the responses to gp120 were high in the absence of an adjuvant. CTA1 was a stronger adjuvant for Gag than was granulocyte-macrophage colony-stimulating factor (GM-CSF), and it also displayed a wider dose range than GM-CSF in mice. In macaques, CTA1 modestly enhanced the antibody responses to SIV Gag but potently primed for a recombinant Gag protein boost. The results of this study show that CTA1 is a potent adjuvant for SIV Gag when delivered by GeneGun in mice and that CTA1 provides a potent GeneGun-mediated DNA prime for a heterologous protein boost in macaques.<\/jats:p>","DOI":"10.1128\/cvi.05019-11","type":"journal-article","created":{"date-parts":[[2011,4,21]],"date-time":"2011-04-21T00:16:16Z","timestamp":1303344976000},"page":"922-930","source":"Crossref","is-referenced-by-count":8,"title":["Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun"],"prefix":"10.1128","volume":"18","author":[{"given":"Kenneth C.","family":"Bagley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George K.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R.","family":"Fouts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2011,4,20]]},"reference":[{"key":"key20180919073517_B1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1046\/j.1440-1711.1998.00750.x","article-title":"A novel concept in mucosal adjuvanticity: the CTA1-DD adjuvant is a B cell-targeted fusion protein that incorporates the enzymatically active cholera toxin A1 subunit","volume":"76","author":"Agren","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"key20180919073517_B2","doi-asserted-by":"crossref","first-page":"6276","DOI":"10.4049\/jimmunol.164.12.6276","article-title":"The ADP-ribosylating CTA1-DD adjuvant enhances T cell-dependent and independent responses by direct action on B cells involving anti-apoptotic Bcl-2- and germinal center-promoting effects","volume":"164","author":"Agren","year":"2000","journal-title":"J. Immunol."},{"key":"key20180919073517_B3","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nbt0998-867","article-title":"Gene transfer into muscle by electroporation in vivo","volume":"16","author":"Aihara","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"key20180919073517_B4","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1128\/JVI.76.9.4536-4546.2002","article-title":"Plasmid vectors encoding cholera toxin or the heat-labile enterotoxin from Escherichia coli are strong adjuvants for DNA vaccines","volume":"76","author":"Arrington","year":"2002","journal-title":"J. Virol."},{"key":"key20180919073517_B5","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1128\/IAI.70.10.5533-5539.2002","article-title":"Cholera toxin and heat-labile enterotoxin activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cyclic AMP-dependent pathway","volume":"70","author":"Bagley","year":"2002","journal-title":"Infect. 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A."},{"key":"key20180919073517_B9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1128\/JVI.71.1.169-178.1997","article-title":"Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2","volume":"71","author":"Chow","year":"1997","journal-title":"J. Virol."},{"key":"key20180919073517_B10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1080\/09687680410001663267","article-title":"Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms","volume":"21","author":"De Haan","year":"2004","journal-title":"Mol. Membr. Biol."},{"key":"key20180919073517_B11","doi-asserted-by":"crossref","first-page":"633","DOI":"10.4049\/jimmunol.175.2.633","article-title":"DNA vaccines: progress and challenges","volume":"175","author":"Donnelly","year":"2005","journal-title":"J. Immunol."},{"key":"key20180919073517_B12","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.4049\/jimmunol.158.5.2278","article-title":"Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization","volume":"158","author":"Feltquate","year":"1997","journal-title":"J. Immunol."},{"key":"key20180919073517_B13","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/nbt0905-1059","article-title":"Rapid-response vaccines\u2014does DNA offer a solution?","volume":"23","author":"Forde","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"key20180919073517_B14","doi-asserted-by":"crossref","first-page":"11478","DOI":"10.1073\/pnas.90.24.11478","article-title":"DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations","volume":"90","author":"Fynan","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"key20180919073517_B15","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1084\/jem.187.7.1123","article-title":"Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity","volume":"187","author":"Giuliani","year":"1998","journal-title":"J. Exp. Med."},{"key":"key20180919073517_B16","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1586\/14760584.6.5.809","article-title":"Transcutaneous immunization with heat-labile enterotoxin: development of a needle-free vaccine patch","volume":"6","author":"Glenn","year":"2007","journal-title":"Expert Rev. 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Arch. Allergy Immunol."},{"key":"key20180919073517_B25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3349\/ymj.1999.40.4.355","article-title":"Administration of multiple cytokine genes with anti-tumor activity inhibits both tumor incidence and tumor growth","volume":"40","author":"Jang","year":"1999","journal-title":"Yonsei Med. J."},{"key":"key20180919073517_B26","doi-asserted-by":"crossref","first-page":"14662","DOI":"10.1073\/pnas.011442598","article-title":"Identification of motifs in cholera toxin A1 polypeptide that are required for its interaction with human ADP-ribosylation factor 6 in a bacterial two-hybrid system","volume":"97","author":"Jobling","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. 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Med."},{"key":"key20180919073517_B32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1586\/14760584.7.2.175","article-title":"Current progress of DNA vaccine studies in humans","volume":"7","author":"Lu","year":"2008","journal-title":"Expert Rev. Vaccines"},{"key":"key20180919073517_B33","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1365-2249.1999.00793.x","article-title":"Macrophage inflammatory protein-1alpha (MIP-1alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1","volume":"115","author":"Lu","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"key20180919073517_B34","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0923-2494(98)80144-2","article-title":"The mechanism of cholera toxin adjuvanticity","volume":"148","author":"Lycke","year":"1997","journal-title":"Res. Immunol."},{"key":"key20180919073517_B35","first-page":"301","article-title":"Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens","volume":"59","author":"Lycke","year":"1986","journal-title":"Immunology"},{"key":"key20180919073517_B36","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1002\/eji.1830220915","article-title":"The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile enterotoxins is linked to their ADP-ribosyltransferase activity","volume":"22","author":"Lycke","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"key20180919073517_B37","first-page":"95","article-title":"Cytokine flow cytometry","volume":"263","author":"Maecker","year":"2004","journal-title":"Methods Mol. Biol."},{"key":"key20180919073517_B38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0022-1759(01)00416-1","article-title":"Use of overlapping peptide mixtures as antigens for cytokine flow cytometry","volume":"255","author":"Maecker","year":"2001","journal-title":"J. Immunol. Methods"},{"key":"key20180919073517_B39","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.clim.2003.11.018","article-title":"Cytokine flow cytometry: a multiparametric approach for assessing cellular immune responses to viral antigens","volume":"110","author":"Maino","year":"2004","journal-title":"Clin. Immunol."},{"key":"key20180919073517_B40","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1089\/aid.1988.4.369","article-title":"Sensitive ELISA for the gp120 and gp160 surface glycoproteins of HIV-1","volume":"4","author":"Moore","year":"1988","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"key20180919073517_B41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/00002030-199004000-00004","article-title":"Characterisation of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and sCD4","volume":"4","author":"Moore","year":"1990","journal-title":"AIDS"},{"key":"key20180919073517_B42","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cyto.a.10038","article-title":"Optimal preparation of rhesus macaque blood for cytokine flow cytometric analysis","volume":"53","author":"Nomura","year":"2003","journal-title":"Cytometry A"},{"key":"key20180919073517_B43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/infdis\/133.Supplement_1.S31","article-title":"Size and structure of the cholera toxin molecule and its subunits","volume":"133","author":"Ohtomo","year":"1976","journal-title":"J. Infect. Dis."},{"key":"key20180919073517_B44","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1590\/S0100-879X1999000200009","article-title":"Immunological properties of gene vaccines delivered by different routes","volume":"32","author":"Oliveira","year":"1999","journal-title":"Braz. J. Med. Biol. Res."},{"key":"key20180919073517_B45","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1074\/jbc.274.7.3962","article-title":"Structural basis for the differential toxicity of cholera toxin and Escherichia coli heat-labile enterotoxin. Construction of hybrid toxins identifies the A2-domain as the determinant of differential toxicity","volume":"274","author":"Rodighiero","year":"1999","journal-title":"J. Biol. Chem."},{"key":"key20180919073517_B46","doi-asserted-by":"crossref","first-page":"5750","DOI":"10.4049\/jimmunol.165.10.5750","article-title":"Modulation of innate and acquired immune responses by Escherichia coli heat-labile toxin: distinct pro- and anti-inflammatory effects of the nontoxic AB complex and the enzyme activity","volume":"165","author":"Ryan","year":"2000","journal-title":"J. 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