Induction of Pulmonary Mucosal Immune Responses With a Protein Vaccine Targeted to the DEC-205/CD205 Receptor

Vaccine. 2012 Oct 5;30(45):6359-67. doi: 10.1016/j.vaccine.2012.08.051. Epub 2012 Sep 1.

Abstract

It is of great interest to develop a pneumonic plague vaccine that would induce combined humoral and cellular immunity in the lung. Here we investigate a novel approach based on targeting of dendritic cells using the DEC-205/CD205 receptor (DEC) via the intranasal route as way to improve mucosal cellular immunity to the vaccine. Intranasal administration of Yersinia pestis LcrV (V) protein fused to anti-DEC antibody together with poly IC as an adjuvant induced high frequencies of IFN-γ secreting CD4(+) T cells in the airway and lung as well as pulmonary IgG and IgA antibodies. Anti-DEC:LcrV was more efficient to induce IFN-γ/TNF-α/IL-2 secreting polyfunctional CD4(+) T cells when compared to non-targeted soluble protein vaccine. In addition, the intranasal route of immunization with anti-DEC:LcrV was associated with improved survival upon pulmonary challenge with the virulent CO92 Y. pestis. Taken together, these data indicate that targeting dendritic cells via the mucosal route is a potential new avenue for the development of a mucosal vaccine against pneumonic plague.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology
  • Antigens, CD / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology*
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunity, Mucosal*
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Lectins, C-Type / immunology*
  • Lung / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Plague / prevention & control*
  • Plague Vaccine / immunology
  • Poly I-C / immunology
  • Poly I-C / pharmacology
  • Pore Forming Cytotoxic Proteins / immunology
  • Receptors, Cell Surface / immunology*
  • Yersinia pestis / pathogenicity

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Antigens, CD
  • DEC-205 receptor
  • Immunoglobulin A
  • Immunoglobulin G
  • LcrV protein, Yersinia
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Plague Vaccine
  • Pore Forming Cytotoxic Proteins
  • Receptors, Cell Surface
  • Interferon-gamma
  • Poly I-C