Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine.
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.
Robinson
Harriet L
HL
Emory Vaccine Center of Emory University School of Medicine, Atlanta, GA 30322, USA. hrobins@rmy.emory.edu
Montefiori
David C
DC
Villinger
Francois
F
Robinson
James E
JE
Sharma
Sunita
S
Wyatt
Linda S
LS
Earl
Patricia L
PL
McClure
Harold M
HM
Moss
Bernard
B
Amara
Rama Rao
RR
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*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor