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Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.

dc.contributor.author Hart, PJ
dc.contributor.author O'Shaughnessy, CM
dc.contributor.author Siggins, MK
dc.contributor.author Bobat, S
dc.contributor.author Kingsley, RA
dc.contributor.author Goulding, DA
dc.contributor.author Crump, John Andrew
dc.contributor.author Reyburn, H
dc.contributor.author Micoli, F
dc.contributor.author Dougan, G
dc.contributor.author Cunningham, AF
dc.contributor.author MacLennan, CA
dc.coverage.spatial United States
dc.date.accessioned 2017-03-02T18:59:14Z
dc.date.available 2017-03-02T18:59:14Z
dc.date.issued 2016
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/26741681
dc.identifier PONE-D-15-38748
dc.identifier.uri http://hdl.handle.net/10161/13763
dc.description.abstract Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies.
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0145945
dc.subject Antibodies, Bacterial
dc.subject Antigens, Bacterial
dc.subject Bacterial Capsules
dc.subject Complement C3
dc.subject Complement Membrane Attack Complex
dc.subject Humans
dc.subject Immune Sera
dc.subject Immunity, Humoral
dc.subject Immunization
dc.subject Lipopolysaccharides
dc.subject Phagocytes
dc.subject Phagocytosis
dc.subject Polysaccharides, Bacterial
dc.subject Primary Cell Culture
dc.subject Salmonella Infections
dc.subject Salmonella typhi
dc.subject Salmonella typhimurium
dc.subject Species Specificity
dc.subject Typhoid Fever
dc.subject Typhoid-Paratyphoid Vaccines
dc.title Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/26741681
pubs.begin-page e0145945
pubs.issue 1
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1932-6203


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