Abstract
The chemokine, lymphotactin (LTN), was tested as a molecular adjuvant using bicistronic DNA vaccines encoding the protective Yersinia capsular (F1) antigen and virulence antigen (V-Ag) as a F1-V fusion protein. The LTN-encoding F1-V or V-Ag vaccines were given by the intranasal (i.n.) or intramuscular (i.m.) routes, and although serum IgG and mucosal IgA antibodies (Abs) were induced, F1-Ag boosts were required for robust anti-F1-Ag Abs. Optimal efficacy against pneumonic plague was obtained in mice i.m.-, not i.n.-immunized with these DNA vaccines. These vaccines stimulated elevated Ag-specific Ab-forming cells and mixed Th cell responses, with Th17 cells markedly enhanced by i.m. immunization. These results show that LTN can be used as a molecular adjuvant to enhance protective immunity against plague.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / genetics
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Administration, Intranasal
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Animals
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Antibodies, Bacterial / analysis
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Antibodies, Bacterial / blood
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology
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Female
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Immunity, Mucosal
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Immunization, Secondary / methods
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Immunoglobulin A / analysis
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Immunoglobulin G / blood
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Injections, Intramuscular
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Lymphokines / administration & dosage
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Lymphokines / genetics
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Mice
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Mice, Inbred BALB C
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Plague / immunology
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Plague / prevention & control*
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Plague Vaccine / administration & dosage*
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Plague Vaccine / genetics
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Plague Vaccine / immunology*
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Pore Forming Cytotoxic Proteins / genetics
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Pore Forming Cytotoxic Proteins / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Sialoglycoproteins / administration & dosage
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Sialoglycoproteins / genetics
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Survival Analysis
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Proteins
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Immunoglobulin A
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Immunoglobulin G
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LcrV protein, Yersinia
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Lymphokines
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Plague Vaccine
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Pore Forming Cytotoxic Proteins
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Recombinant Fusion Proteins
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Sialoglycoproteins
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Vaccines, DNA
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Vaccines, Synthetic
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caf1 protein, Yersinia pestis
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lymphotactin