Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4⁺ and CD8⁺ T lymphocyte responses

Abstract

The immunogenicity of plasmid DNA vaccines may be limited by the availability of professional antigen-presenting cells (APC) at the site of inoculation. Here we demonstrate that the types of APC recruited to the injection site can selectively modulate CD4 + or CD8 + T lymphocyte responses elicited by an HIV-1 Env DNA vaccine in mice. Coadministration of plasmid GM-CSF with the DNA vaccine resulted in the recruitment of macrophages to the site of inoculation and specifically augmented vaccine-elicited CD4 + T lymphocyte responses. In contrast, coadministration of plasmid MIP-1 § with the DNA vaccine resulted in the recruitment of dendritic cells to the injection site and enhanced vaccine-elicited CD8 + T lymphocyte responses. Interestingly, coadministration of both plasmid GM-CSF and plasmid MIP-1 § with the DNA vaccine recruited both macrophages and dendritic cells and led to a synergistic and sustained augmentation of CD4 + and CD8 + T lymphocyte responses. These data demonstrate the critical importance of locally recruited professional APC in determining the magnitude and nature of immune responses elicited by plasmid DNA vaccines. Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses.

Plasmid DNA Vaccine-Elicited Cellular Immune Responses Limit In Vivo Vaccine Antigen Expression through Fas-Mediated Apoptosis

“…Loss of vaccine Ag expression in the wild-type mice became apparent at approximately the same time that Ag-specific T cell immune responses to these immunogens are reported to be first detectable (27,28). To assess the kinetics of the emergence of immune responses elicited by plasmid DNA and recombinant adenovirus, we immunized mice with vectors encoding gp120 and prospectively measured p18 tetramer responses (data not shown).…”

Fusion to Listeriolysin O and Delivery by Listeria monocytogenes Enhances the Immunogenicity of HER-2/neu and Reveals Subdominant Epitopes in the FVB/N Mouse

“…with Lm-LLO-EC1 or PBS on days 3, 10, and 18. GM-CSF was included as an adjuvant for the DNA vaccines because of its ability to enhance the efficacy of DNA vaccines (29). The best vaccine based on this experiment was Lm-LLO-EC1 (Fig.…”

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

“…The redirection of systemic immune cells in vivo by DNA vaccination using chemokines as part of a DNA-encoded vaccine cocktail has been previously reported. 23,24 Chemokines are inflammatory molecules that act primarily as chemoattractants and as activators of lymphocytes through the enhancement of Th1 and Th2 phenotypes. [23][24][25][26][27] Thus, modulation of immune responses through the chemokine network is an interesting concept for vaccine design.…”