Enhanced potency of plasmid DNA microparticle human immunodeficiency virus vaccines in rhesus macaques by using a priming-boosting regimen with recombinant proteins.
DNA vaccines have been used widely in experimental primate models of human immunodeficiency virus (HIV), but their effectiveness has been limited. In this study, we evaluated three technologies for increasing the potency of DNA vaccines in rhesus macaques. These included DNA encoding Sindbis virus RNA replicons (pSINCP), cationic poly(lactide-co-glycolide) (PLG) microparticles for DNA delivery, and recombinant protein boosting. The DNA-based pSINCP replicon vaccines encoding HIV Gag and Env were approximately equal in potency to human cytomegalovirus (CMV) promoter-driven conventional DNA vaccines (pCMV). The PLG microparticle DNA delivery system was particularly effective at enhancing antibody responses induced by both pCMV and pSINCP vaccines and had less effect on T cells. Recombinant Gag and Env protein boosting elicited rapid and strong recall responses, in some cases to levels exceeding those seen after DNA or DNA/PLG priming. Of note, Env protein boosting induced serum-neutralizing antibodies and increased frequencies of gamma interferon-producing CD4 T cells severalfold. Thus, PLG microparticles are an effective means of delivering DNA vaccines in nonhuman primates, as demonstrated for two different types of DNA vaccines encoding two different antigens, and are compatible for use with DNA prime-protein boost regimens.
Otten
Gillis R
GR
Chiron Corporation, 4560 Horton St., Mail Stop 4.3, Emeryville, California 94608, USA. gillis_otten@chiron.com
Schaefer
Mary
M
Doe
Barbara
B
Liu
Hong
H
Srivastava
Indresh
I
Megede
Jan zur
Jz
Kazzaz
Jina
J
Lian
Ying
Y
Singh
Manmohan
M
Ugozzoli
Mildred
M
Montefiori
David
D
Lewis
Mark
M
Driver
David A
DA
Dubensky
Thomas
T
Polo
John M
JM
Donnelly
John
J
O'Hagan
Derek T
DT
Barnett
Susan
S
Ulmer
Jeffrey B
JB
D016915:AIDS Vaccines; D000818:Animals; D004279:DNA, Viral / Q000494:pharmacology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D010957:Plasmids / Q000235:genetics*; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA; D014764:Viral Proteins / Q000276:immunology
D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins