The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children
Calman A. MacLennan, Esther N. Gondwe, Chisomo L. Msefula, Robert A. Kingsley, Nicholas R. Thomson, Sarah A. White, Margaret Goodall, Derek J. Pickard, Stephen M. Graham, Gordon Dougan, C. Anthony Hart, Malcolm E. Molyneux, Mark T. Drayson
Calman A. MacLennan, Esther N. Gondwe, Chisomo L. Msefula, Robert A. Kingsley, Nicholas R. Thomson, Sarah A. White, Margaret Goodall, Derek J. Pickard, Stephen M. Graham, Gordon Dougan, C. Anthony Hart, Malcolm E. Molyneux, Mark T. Drayson
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Research Article Immunology

The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children

Abstract

Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cell-mediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody.

Authors

Calman A. MacLennan, Esther N. Gondwe, Chisomo L. Msefula, Robert A. Kingsley, Nicholas R. Thomson, Sarah A. White, Margaret Goodall, Derek J. Pickard, Stephen M. Graham, Gordon Dougan, C. Anthony Hart, Malcolm E. Molyneux, Mark T. Drayson

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Figure 10

Age-based comparison of healthy Malawian children with cases of NTS bacteremia in Malawian children: serum bactericidal activity and serum anti-Salmonella IgG and IgM titers.

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Killing of NTS and anti-Salmonella IgG and IgM titers for serum from Mal...
Serological data are from 65 Malawian children as shown in Figure 4 grouped by age (0–6, 6–12, 12–18, and 18–24 months; 2–3, 3–4, 4–5, and 5–10 years). Shown are mean and 95% CI serum bactericidal activity against S. Typhimurium isolate D23580 at 180 minutes (solid line) and geometric mean and 95% CI anti-D23580 IgG (short dashes) and IgM (long dashes) titers. Below, age distribution of NTS bacteremia cases is reproduced from Figure 1 for reference.