Yersinia pestis YadC: a novel vaccine candidate against plague.
Current subunit vaccines provide partial protection against pneumonic plague if the infecting Y. pestis strain is encapsulated (F1+). Here we describe YadC, a novel Y. pestis outer membrane protein that provides partial protection against a F1(-) Y. pestis strain. Swiss-Webster mice were immunized subcutaneously with glutathione S-transferase (GST) or His6-tagged (HT) purified fusion proteins (GST-YadC137-409 or HT-LcrV) or buffer emulsified with Alhydrogel. Intravenous challenge with 1 x 10(4) F1(-) Deltapgm Y. pestis CO99-3015 revealed no protection for those mice immunized with GST-Alhydrogel alone, full protection for HT-LcrV-immunized mice, and partial protection for GST-YadC137-409-immunized mice. Similarly, C57BL/6 mice were immunized with GST-YadC137-409, HT-LcrV, or GST all with Alhydrogel adjuvant. After intranasal challenge with 3 x 10(3) F1(-) Y. pestis CO99-3015, 87% of GST-YadC137-409-immunized mice survived pneumonic plague. This is compared to the GST control group (0 surviving mice) and the LcrV-immunized group where 50% survived the challenge. This protection was correlated with a predominantly IgG1 response in LcrV-immunized mice and an IgG1/IgG3 antibody response in YadC-immunized mice. Additionally, we report the cytokine response from HT-LcrV- and GST-YadC137-409-stimulated peripherally derived macrophages. YadC-stimulated cells demonstrated a predominant pro-inflammatory cytokine production. This mixed Thl/Th2 response suggests that YadC's protection may involve a different adaptive immune response than the LcrV protein that currently is part of plague vaccines.
Murphy
Brian S
BS
Department of Internal Medicine, University of Kentucky, Lexington, USA. bsmurp1@uky.edu
Wulff
Christine R
CR
Garvy
Beth A
BA
Straley
Susan C
SC
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009876:Operon; D010930:Plague / Q000276:immunology / Q000517:prevention & control; D010931:Plague Vaccine / Q000235:genetics* / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000382:microbiology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D017931:DNA Primers; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D010931:Plague Vaccine; D022223:Vaccines, Subunit