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.
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=or<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.
Lai
Lilin
L
Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA; Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30322, USA.
Vödrös
Dalma
D
Kozlowski
Pamela A
PA
Montefiori
David C
DC
Wilson
Robert L
RL
Akerstrom
Vicki L
VL
Chennareddi
Lakshmi
L
Yu
Tianwei
T
Kannanganat
Sunil
S
Ofielu
Lazarus
L
Villinger
Francois
F
Wyatt
Linda S
LS
Moss
Bernard
B
Amara
Rama Rao
RR
Robinson
Harriet L
HL
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D012007:Rectum / Q000276:immunology*; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000517:prevention & control; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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