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

Luciana Barros De Arruda, Priya R. Chikhlikar, Thomas August, Ernesto T A Marques

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalImmunology
Volume112
Issue number1
DOIs
StatePublished - May 2004

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Lysosome-Associated Membrane Glycoproteins
DNA Vaccines
Long-Term Memory
Major Histocompatibility Complex
HIV-1
Immunologic Memory
Immunization
DNA
T-Lymphocytes
gag Gene Products
Secondary Immunization
CD4 Antigens
Vaccinia virus
Antigen Presentation
Helper-Inducer T-Lymphocytes
B-Lymphocytes
Antigens

Keywords

  • Immunological memory: T-cell memory
  • MHC II: Trafficking
  • Vaccines: DNA LAMP/Gag, prime/boost immunizations

ASJC Scopus subject areas

  • Immunology

Cite this

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. / De Arruda, Luciana Barros; Chikhlikar, Priya R.; August, Thomas; Marques, Ernesto T A.

In: Immunology, Vol. 112, No. 1, 05.2004, p. 126-135.

Research output: Contribution to journalArticle

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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.",
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