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Vaccine. 2010 Feb 3;28(5):1300-9. doi: 10.1016/j.vaccine.2009.11.020. Epub 2009 Nov 26.

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.

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Department of Microbiology and Immunology, Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.


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.

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