Vaccine-induced antibodies are sufficient to limit Salmonella infection in the absence of complement or macrophages.

Antibodies to Salmonella Typhimurium (STm) can protect against infection. Understanding better how antibodies, complement, and leukocytes interplay can support vaccine development. We used an Outer Membrane Vesicle (OMV) vaccine against STm to study the in vivo function of anti-STm antibodies. Using intravital microscopy, we found that upon challenge, OMV-specific antibodies promote STm uptake by spleen and liver macrophages, with neutrophils rarely capturing the bacteria. Clodronate-liposome depletion of monocytic cells reveals that these cells help prevent antigen dissemination. After vaccination and challenge of C1q, C3, C4, and C5-deficient mice, all mice except C3-deficient were protected by OMV immunization. C3-deficient mice failed to mount significant germinal center and plasma cell responses; however, after the adoptive transfer of immune sera, they had lower bacterial burdens than controls. In vitro, we showed that antibodies enhance bacterial capture in macrophages. Thus, antibodies alone are sufficient to reduce bacterial burdens, but they cooperate with complement and macrophages to maximize their functions in vivo.