Anaplasma marginaleType IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine
- 1 March 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (3), 1314-1325
- https://doi.org/10.1128/iai.01207-09
Abstract
Anaplasmaand relatedEhrlichiaspp. are important tick-borne, Gram-negative bacterial pathogens of livestock and humans that cause acute infection and disease and can persist. Immunization of cattle with anAnaplasma marginalefraction enriched in outer membranes (OM) can provide complete protection against disease and persistent infection. Serological responses of OM vaccinees to the OM proteome previously identified over 20 antigenic proteins, including three type IV secretion system (T4SS) proteins, VirB9-1, VirB9-2, and VirB10. Subsequent studies showed that these three proteins also stimulated CD4+T-cell responses in OM vaccinees. The T4SS, composed of a complex of proteins spanning the inner and outer membranes of certain bacteria, is an important virulence factor but is relatively unexplored as a vaccine target. The goal of this study was to determine if additional T4SS proteins are immunogenic for animals immunized with the protective OM fraction ofA. marginale.T4SS proteins expressed byin vitrotranscription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins inEscherichia coliand their immunogenicity was verified. VirB2, a putative VirB7, VirB11, and VirD4 were immunogenic for OM vaccinees expressing several common major histocompatibility complex (MHC) class II haplotypes. VirB2 is encoded by multiple genes that share a conserved central region, and epitope mapping revealed T-cell epitopes in this region. The discovery of novel immunogenic T4SS proteins recognized by outbred individuals with common MHC haplotypes further justifies evaluating the T4SS as a potential vaccine candidate for pathogenic bacteria.Keywords
This publication has 72 references indexed in Scilit:
- Structure of a Type IV Secretion System Core ComplexScience, 2009
- VirB3 to VirB6 and VirB8 to VirB11, but Not VirB7, Are Essential for Mediating Persistence ofBrucellain the Reticuloendothelial SystemJournal of Bacteriology, 2008
- Composition of the Surface Proteome ofAnaplasma marginaleand Its Role in Protective Immunity Induced by Outer Membrane ImmunizationInfection and Immunity, 2008
- Protein Subassemblies of theHelicobacter pyloriCag Type IV Secretion System Revealed by Localization and Interaction StudiesJournal of Bacteriology, 2008
- Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances ImmunogenicityInfection and Immunity, 2008
- Identification of Novel Surface Proteins ofAnaplasma phagocytophilumby Affinity Purification and ProteomicsJournal of Bacteriology, 2007
- Immunogenicity of Anaplasma marginale Type IV Secretion System Proteins in a Protective Outer Membrane VaccineInfection and Immunity, 2007
- NMR structure of a complex between the VirB9/VirB7 interaction domains of the pKM101 type IV secretion systemProceedings of the National Academy of Sciences of the United States of America, 2007
- Characterization of the Pilin Ortholog of theHelicobacter pyloriType IVcagPathogenicity Apparatus, a Surface-Associated Protein Expressed during InfectionJournal of Bacteriology, 2006
- The versatile bacterial type IV secretion systemsNature Reviews Microbiology, 2003