Adjuvantive effects of anti-4-1BB agonist Ab and 4-1BBL DNA for a HIV-1 Gag DNA vaccine: different effects on cellular and humoral immunity.
Plasmid DNA immunizations induce low levels but a broad spectrum of cellular and humoral immune responses. Here, we investigate the potential of co-stimulation through 4-1BB as an adjuvant for a HIV-1 DNA vaccine in mice. We designed plasmid DNAs expressing either the membrane bound or soluble form of 4-1BBL, and compared with the agonistic anti-4-1BB Ab for their ability to adjuvant the Gag DNA vaccine. Both, anti-4-1BB agonistic Ab as well as 4-1BBL DNA enhanced the Gag-specific cellular immune responses. However, in complete contrast to the agonistic Ab that suppressed humoral immunity to Gag, 4-1BBL DNA adjuvanted vaccines enhanced Gag-specific IgG responses. Importantly, the expression of Gag and 4-1BBL from the same plasmid was critical for the adjuvant activity. Collectively, our data suggest that for a HIV-1 vaccine where both antigen-specific cellular and humoral immunity are desirable, 4-1BBL expressed by a DNA vaccine is a superior adjuvant than anti-4-1BB agonistic Ab.
Ganguly
Sumita
S
Department of Microbiology and Immunology, Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Liu
Jinyan
J
Pillai
Vinod B
VB
Mittler
Robert S
RS
Amara
Rama Rao
RR
D053330:4-1BB Ligand / Q000235:genetics / Q000276:immunology*; D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D053330:4-1BB Ligand; D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus