DNA vaccine encoding human immunodeficiency virus‐1 Gag, targeted to the major histocompatibility complex II compartment by lysosomal‐associated membrane protein, elicits enhanced long‐term memory response

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Abstract
Antigen presentation by major histocompatibility complex type II (MHC II) molecules and activation of CD4+ helper T cells are critical for the generation of immunological memory. We previously described a DNA vaccine encoding human immunodeficiency virus-1 p55Gag as a chimera with the lysosome-associated membrane protein (LAMP/gag). The LAMP/gag chimera protein traffics to the MHC II compartment of transfected cells and elicits enhanced immune responses as compared to a DNA vaccine encoding native gag not targeted to the MHC II compartment. We have now investigated the long-term responses of immunized mice and show that the LAMP/gag DNA vaccine promotes long-lasting B cell- and CD4+ and CD8+ T-cell memory responses and elicits a potent Gag-specific CD8+ recall response to challenge with vaccinia virus encoding gag, even 11 months after immunization. In contrast, the immune responses induced by DNA encoding non-targeted Gag decay rapidly and elicit very low or undetectable levels of Gag-specific CD4+ and CD8+ memory cells. A single priming immunization with LAMP/gag DNA is sufficient to generate T-cell memory. Following this initial priming immunization with LAMP/gag DNA, booster immunizations with native gag DNA or the LAMP/gag chimera are equally efficient in eliciting B- and T-cell secondary responses, results in accordance with observations that secondary expansion of CD8+ cells in the boost phase does not require additional CD4+ help. These findings underscore the significance of targeting DNA-encoded vaccine antigens to the MHC II processing compartments for induction of long-term immunological memory.