Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non-Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae

J Immunol. 2020 Feb 15;204(4):903-913. doi: 10.4049/jimmunol.1901184. Epub 2020 Jan 8.


Plasmid DNA is a promising vaccine platform that together with electroporation can elicit significant systemic Ab responses; however, immunity at mucosal sites remains low. In this study, we sought to program T and B cells to home to the gastrointestinal and vaginal mucosae using genetic chemokine adjuvants and assessed their impact on immune homeostasis in various distinct immune compartments. BALB/c mice were immunized i.m. with plasmid DNA encoding a model Ag HIV-1 Env gp140 and selected chemokines/cytokine and boosted intravaginally with gp140 recombinant protein. Isolated splenocytes, intestinal lymphocytes, and genital lymphocytes as well as serum and intestinal luminal contents were assessed for Ag-specific reactivity. In addition, flow cytometric analysis was performed to determine the impact on immune homeostasis at these sites. Different molecular chemokine/cytokine adjuvants effected significant alterations to the recruitment of B and T cells to the spleen, vaginal and intestinal mucosae, for example CCL25 enhanced splenic and vaginal Ag-specific T cell responses whereas CCL28 increased the levels of specific T cells only in the vaginal mucosa. The levels of Ab could be modulated in the systemic circulation, as well as the vaginal vault and intestinal lumen, with CCL20 playing a central role. Our data demonstrate that the CCL20, CCL25, and CCL28 genetic chemokine adjuvants enhance the vaccine Ag-specific humoral and cellular responses and induce homing to the intestinal and female genital mucosae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / genetics
  • Animals
  • B-Lymphocytes / immunology
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Female
  • HEK293 Cells
  • HIV Antigens / genetics
  • HIV Antigens / immunology
  • HIV Infections / prevention & control
  • HIV-1 / genetics
  • HIV-1 / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Intestinal Mucosa / immunology*
  • Mice
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Plasmids / immunology
  • T-Lymphocytes / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vagina / immunology*
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Chemokines, CC
  • HIV Antigens
  • Vaccines, DNA
  • env Gene Products, Human Immunodeficiency Virus
  • gp140 envelope protein, Human immunodeficiency virus 1