Antibody-based approaches to
pneumococcal disease may hold promise for immunocompromised patients in whom
vaccines are less immunogenic and/or in the context of antimicrobial resistance. Antibody-mediated protection against experimental
pneumococcal pneumonia has been shown to depend on immunoregulation, but the relationship between antibody and protection against pneumococcal
sepsis and immunoregulation has not been examined. Similarly, the requirement for B and T cells for antibody efficacy is not known. In this study, we determined the efficacy of the human pneumococcal capsular
polysaccharide serotype 3-specific antibody, A7 (
immunoglobulin M [
IgM]), in
secretory IgM (sIgM)(-/-), CD4(-/-), CD8(-/-), muMT(-/-), and SCID mice and investigated its effect on
cytokine and
chemokine expression in sera and spleens from mice with intact cellular immunity. A7 is known to be protective against systemic
infection with serotype 3 and to require
complement for efficacy. Compared to that of an isotype control antibody, A7 administration prolonged the survival of mice of each immunodeficient strain and was associated with a significant reduction in CFU in blood, lung, and spleen samples and a significantly reduced level of keratinocyte-derived
chemokine (KC),
interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2) expression in normal and sIgM(-/-) mice. Studies with mice treated with
penicillin revealed similar reductions in CFU and similar levels of
IL-6, KC, or MIP-2 expression in A7- and
penicillin-treated mice. These findings demonstrate that natural
IgM and B and T cells are dispensable for A7-mediated protection against experimental pneumococcal
sepsis and suggest that the efficacy of antibody-mediated protection depends on
immunomodulation. Taken together, our data extend the association between antibody-mediated protection and
immunomodulation to protection against systemic
pneumococcal infection and to a clinically important serotype often responsible for pneumococcal
sepsis.