A comparative study of the treatment of tularemia with immune serum, hyperimmune serum and streptomycin

Foshay, Lee

doi:10.1016/0002-9343(46)90036-8

Cited by 31 publications

(21 citation statements)

References 4 publications

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“…Similar to the results presented here, there is a growing appreciation of the significant role Abs play in the control and clearance of other intracellular pathogens (26). In the case of F. tularensis, although heterologous antisera were extensively used to treat human tularemia with significant success before antibiotics were discovered (27), more recently, B cells but not Abs were reported to be critical for systemic protection (9). Nevertheless, adoptive transfer of serum Abs has been shown by others (10 -13) to significantly reduce bacterial numbers in the spleen and liver in systemic disease models.…”

Section: Discussionsupporting

confidence: 61%

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

Kirimanjeswara

Golden

Bakshi

et al. 2007

The Journal of Immunology

103

142

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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.

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Section: Discussionsupporting

confidence: 61%

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

Kirimanjeswara

Golden

Bakshi

et al. 2007

The Journal of Immunology

103

142

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“…This finding stimulated Foshay to work to develop a killed tularemia vaccine that induced humoral immunity (54,55). A number of techniques were employed to prepare the killed bacterial cells, including heating, acetone, and phenol treatment, and the Foshay vaccines were administered to human volunteers with variable results.…”

Section: Development Of Nonliving Tularemia Vaccinesmentioning

confidence: 99%

Tularemia

et al. 2002

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Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia

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“…Passive protection against tularemia has been demonstrated for a long time (18). 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).…”

mentioning

confidence: 99%

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

Savitt

Mena-Taboada

Monsalve

et al. 2009

Clin Vaccine Immunol

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Francisella tularensis is the causative agent of tularemia and a potential agent of biowarfare. As an easily transmissible infectious agent, rapid detection and treatment are necessary to provide a positive clinical outcome. As an agent of biowarfare, there is an additional need to prevent infection. We made monoclonal antibodies to the F. tularensis subsp. holarctica live vaccine strain (F. tularensis LVS) by infecting mice with a sublethal dose of bacteria and, following recovery, by boosting the mice with sonicated organisms. The response to the initial and primary infection was restricted to immunoglobulin M antibody directed solely against lipopolysaccharide (LPS). After boosting with sonicated organisms, the specificity repertoire broadened against protein antigens, including DnaK, LpnA, FopA, bacterioferritin, the 50S ribosomal protein L7/L12, and metabolic enzymes. These monoclonal antibodies detect F. tularensis LVS by routine immunoassays, including enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence. The ability of the antibodies to protect mice from intradermal infection, both prophylactically and therapeutically, was examined. An antibody to LPS which provides complete protection from infection with F. tularensis LVS and partial protection from infection with F. tularensis subsp. tularensis strain SchuS4 was identified. There was no bacteremia and reduced organ burden within the first 24 h when mice were protected from F. tularensis LVS infection with the anti-LPS antibody. No antibody that provided complete protection when administered therapeutically was identified; however, passive transfer of antibodies against LPS, FopA, and LpnA resulted in 40 to 50% survival of mice infected with F. tularensis LVS.

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A comparative study of the treatment of tularemia with immune serum, hyperimmune serum and streptomycin

Cited by 31 publications

References 4 publications

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

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

Tularemia

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

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