Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies

M. A. Lindorfer, A. Nardin, P. L. Foley, M. D. Solga, A. J. Bankovich, E. N. Martin, A. L. Henderson, C. W. Price, E. Gyimesi, C. P. Wozencraft, J. B. Goldberg, W. M. Sutherland, R. P. Taylor

Research output: Contribution to journalArticle

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Abstract

We examined the ability of a bispecific mAb reagent, consisting of a mAb specific for the primate erythrocyte complement receptor cross-linked with an anti-bacterial mAb, to target bacteria in the bloodstream in an acute infusion model in monkeys. In vitro studies demonstrated a variable level of complement-mediated binding (immune adherence) of Pseudomonas aeruginosa (strain PAO1) to primate E in serum. In vivo experiments in animals depleted of complement revealed that binding of bacteria to E was 99% of the bacteria bound to E. In complement-replete monkeys, a variable fraction of infused bacteria bound to E. This finding may have significant implications in the interpretation of animal models and in the understanding of bacteremias in humans. Treatment of these complement-replete monkeys with the bispecific reagent led to >99% binding of bacteria to E. Twenty-four-hour survival studies were conducted; several clinical parameters, including the degree of lung damage, cytokine levels, and liver enzymes in the circulation, indicate that the bispecific mAb reagent provides a degree of protection against the bacterial challenge.

Original languageEnglish
Pages (from-to)2240-2249
Number of pages10
JournalJournal of Immunology
Volume167
Issue number4
Publication statusPublished - Aug 15 2001

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Bispecific Antibodies
Pseudomonas aeruginosa
Bacteria
Haplorhini
Primates
Complement Receptors
Bacteremia
Animal Models
Erythrocytes
Cytokines
Lung
Survival
Liver
Enzymes
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Lindorfer, M. A., Nardin, A., Foley, P. L., Solga, M. D., Bankovich, A. J., Martin, E. N., ... Taylor, R. P. (2001). Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies. Journal of Immunology, 167(4), 2240-2249.

Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies. / Lindorfer, M. A.; Nardin, A.; Foley, P. L.; Solga, M. D.; Bankovich, A. J.; Martin, E. N.; Henderson, A. L.; Price, C. W.; Gyimesi, E.; Wozencraft, C. P.; Goldberg, J. B.; Sutherland, W. M.; Taylor, R. P.

In: Journal of Immunology, Vol. 167, No. 4, 15.08.2001, p. 2240-2249.

Research output: Contribution to journalArticle

Lindorfer, MA, Nardin, A, Foley, PL, Solga, MD, Bankovich, AJ, Martin, EN, Henderson, AL, Price, CW, Gyimesi, E, Wozencraft, CP, Goldberg, JB, Sutherland, WM & Taylor, RP 2001, 'Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies', Journal of Immunology, vol. 167, no. 4, pp. 2240-2249.
Lindorfer MA, Nardin A, Foley PL, Solga MD, Bankovich AJ, Martin EN et al. Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies. Journal of Immunology. 2001 Aug 15;167(4):2240-2249.
Lindorfer, M. A. ; Nardin, A. ; Foley, P. L. ; Solga, M. D. ; Bankovich, A. J. ; Martin, E. N. ; Henderson, A. L. ; Price, C. W. ; Gyimesi, E. ; Wozencraft, C. P. ; Goldberg, J. B. ; Sutherland, W. M. ; Taylor, R. P. / Targeting of Pseudomonas aeruginosa in the bloodstream with bispecific monoclonal antibodies. In: Journal of Immunology. 2001 ; Vol. 167, No. 4. pp. 2240-2249.
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