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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
Author(s) -
De Arruda Luciana Barros,
Chikhlikar Priya R.,
August J. Thomas,
Marques Ernesto T. A.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01823.x
Subject(s) - biology , dna vaccination , virology , group specific antigen , priming (agriculture) , major histocompatibility complex , cd8 , immune system , antigen , cross presentation , t cell , antigen presentation , immunology , virus , immunization , botany , germination
Summary 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.