title: Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine.
abstract: Here, we use a vaccine consisting of DNA priming followed by MVA boosting in rhesus macaques to investigate the ability of GM-CSF DNA to serve as an adjuvant for the elicitation of neutralizing Ab against an HIV-1 Env. The trial used Gag, Pol, and Env sequences from SHIV-89.6 in the immunogens and a neutralization escape variant of SHIV-89.6, SHIV-89.6P, for challenge. Co-delivery of GM-CSF and vaccine DNAs enhanced the temporal appearance of neutralizing Ab and broadened the specificity of the neutralizing activity to include SHIV-89.6P. Two long-term SHIV-89.6 infections elicited neutralizing activity for SHIV-89.6 but not SHIV-89.6P. Studies on the avidity of the anti-Env antisera revealed that the GM-CSF-adjuvanted vaccine had elicited higher avidity Ab than the non-adjuvanted vaccine or the infection. The GM-CSF-adjuvanted group showed a trend towards better control of the challenge infection and had better control of re-emergent virus (P < 0.01) than the non-adjuvanted group.
authors.affiliation: Emory Vaccine Center of Emory University School of Medicine, Atlanta, GA 30322, USA. hrobins@rmy.emory.edu
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Harold M
authors.initials: HM
authors.lastname: McClure
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000915:Antibody Affinity; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor