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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.

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