GM-CSF DNA:: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine

被引:67
作者
Lai, Lilin
Vodros, Dalma
Kozlowski, Pamela A.
Montefiori, David C.
Wilson, Robert L.
Akerstrom, Vicki L.
Chennareddi, Lakshmi
Yu, Tianwei
Kannanganat, Sunil
Ofielu, Lazarus
Villinger, Francois
Wyatt, Linda S.
Moss, Bernard
Amara, Rama Rao
Robinson, Harriet L.
机构
[1] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[2] Emory Vaccine Ctr, Atlanta, GA 30322 USA
[3] LSUHSC, Gene Therapy Program, New Orleans, LA 70112 USA
[4] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[5] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA
[6] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[7] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA
关键词
immunodeficiency virus; vaccine; GM-CSF adjuvant; ab avidity; rectal IgA;
D O I
10.1016/j.virol.2007.07.017
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Single intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian-human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both the blood and intestines against the acute phase of an intrarectal SHIV-89.6P challenge. GM-CSF appeared to contribute to protection by enhancing two antibody responses: the avidity maturation of anti-Env IgG in blood (p=<0.01) and the presence of long lasting anti-viral IgA in rectal secretions (p<0.01). The avidity of anti-Env IgG showed strong correlations with protection both pre and post challenge. Animals with the highest avidity anti-Env Ab had 1000-fold reductions in peak viremia over those with the lowest avidity anti-Env Ab. The enhanced IgA response was associated with the best protection, but did not achieve significance. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:153 / 167
页数:15
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