Augmentation of immune responses to HIV-1 and simian immunodeficiency virus DNA vaccines by IL-2/Ig plasmid administration in rhesus monkeys

The potential utility of plasmid DNA as an HIV-1 vaccination modality curre ntly is an area of active investigation. However, recent studies have raise d doubts as to whether plasmid DNA alone will elicit immune responses of su fficient magnitude to protect against pathogenic AIDS virus challenges. We therefore investigated whether DNA vaccine-elicited immune responses in rhe sus monkeys could he augmented by using either an IL-2/lg fusion protein or a plasmid expressing IL-2/lg. Sixteen monkeys, divided into four experimen tal groups, were immunized with (i) sham plasmid, (ii) HIV-1 Env 89.6P and simian immunodeficiency virus mac239 Gag DNA vaccines alone, (iii) these DN A vaccines and IL-2/lg protein, or (iv) these DNA vaccines and IL-2/lg plas mid. The administration of both IL-2/lg protein and IL-2/lg plasmid induced a significant and:sustained in vivo activation of peripheral T cells in th e vaccinated monkeys. The monkeys that received IL-2/lg plasmid generated 3 0-fold higher Env-specific antibody titers and 5-fold higher Gag-specific, tetramer-positive CD8+ T cell levels than the monkeys receiving the DNA vac cines alone. IL-2/lg protein also augmented the vaccine-elicited immune res ponses, but less effectively than IL-2/lg plasmid. Augmentation of the immu ne responses by IL-2/lg was evident after the primary immunization and incr eased with subsequent boost immunizations. These results demonstrate that t he administration of IL-2/lg plasmid can substantially augment vaccine-elic ited humoral and cellular immune responses in higher primates.