Prophylactic and Therapeutic Use of Antibodies for Protection against Respiratory Infection with Francisella tularensis

Abstract

The role of Abs in protection against respiratory infection with the intracellular bacterium Francisella tularensis is not clear. To investigate the ability of Abs to clear bacteria from the lungs and prevent systemic spread, immune serum was passively administered i.p. to naive mice before intranasal F. tularensis live vaccine strain infection. It was found that immune serum treatment provided 100% protection against lethal challenge while normal serum or Ig-depleted immune serum provided no protection. Protective efficacy was correlated with increased clearance of bacteria from the lung and required expression of FcγR on phagocytes, including macrophages and neutrophils. However, complement was not required for protection. In vitro experiments demonstrated that macrophages were more readily infected by Ab-opsonized bacteria but became highly efficient in killing upon activation by IFN-γ. Consistent with this finding, in vivo Ab-mediated protection was found to be dependent upon IFN-γ. SCID mice were not protected by passive Ab transfer, suggesting that T cells but not NK cells serve as the primary source for IFN-γ. These data suggest that a critical interaction of humoral and cellular immune responses is necessary to provide sterilizing immunity against F. tularensis. Of considerable interest was the finding that serum Abs were capable of conferring protection against lethal respiratory tularemia when given 24–48 h postexposure. Thus, this study provides the first evidence for the therapeutic use of Abs in Francisella-infected individuals.

Tularemia: A General Overview on Current Treatment Options

“…Temastan iki gün içinde imm ün serum verildiğin-de koruyucudur. Tularemi etkenine maruz kalan farelere normal serum veya immünoglobulin içermeyen serumlar verildiğinde koruyucu olmadığı görülmüştür (56). Bu veriler immün serumun hem tedavi hem de temas sonrası profilaktik uygulama için olası rolünü göstermekle birlikte, bu sonuçların diğer tularemi infeksiyon modellerinde de desteklenmesi gereklidir.…”

Francisella tularensisInfection-Derived Monoclonal Antibodies Provide Detection, Protection, and Therapy

“…Transfer of peritoneal leukocytes and serum from immune mice into naïve mice resulted in survival of 10% of the mice when challenged with fully virulent F. tularensis SchuS4; rechallenged 6 weeks later, all the surviving mice died (1). However, more than 40 years later, there have been only a few studies that investigated the ability of passively transferred antibodies to protect against infection, with results demonstrating that immune serum may be protective in the presence of a coordinated host response (21,30,52,53).…”

Tularemia: current diagnosis and treatment options

“…As mentioned previously, transfer of serum from mice immunized against F. tularensis protected mice challenged in a LVS respiratory infection model [35]. Normal sera or immunoglobulin-deplete sera were not protective.…”

“…Other reviews have suggested that passive immune transfer may be useful in certain circumstances [34]. A recent study in mice demonstrated the passive immunization of immune serum-protected mice in a LVS infection model [35]. Further study on the role of antibodies in protection against tularemia infection is important for both vaccine development and possible therapeutic products.…”