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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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