Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays

Mary Ann Pohl, Johanna Rivera, Antonio Nakouzi, Siu Kei Chow, Arturo Casadevall

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Monoclonal antibodies (MAbs) are potential therapeutic agents against Bacillus anthracis toxins, since there is no current treatment to counteract the detrimental effects of toxemia. In hopes of isolating new protective MAbs to the toxin component lethal factor (LF), we used a strain of mice (C57BL/6) that had not been used in previous studies, generating MAbs to LF. Six LF-binding MAbs were obtained, representing 3 IgG isotypes and one IgM. One MAb (20C1) provided protection from lethal toxin (LeTx) in an in vitro mouse macrophage system but did not provide significant protection in vivo. However, the combination of two MAbs to LF (17F1 and 20C1) provided synergistic increases in protection both in vitro and in vivo. In addition, when these MAbs were mixed with MAbs to protective antigen (PA) previously generated in our laboratory, these MAb combinations produced synergistic toxin neutralization in vitro. But when 17F1 was combined with another MAb to LF, 19C9, the combination resulted in enhanced lethal toxicity. While no single MAb to LF provided significant toxin neutralization, LF-immunized mice were completely protected from infection with B. anthracis strain Sterne, which suggested that a polyclonal response is required for effective toxin neutralization. In total, these studies show that while a single MAb against LeTx may not be effective, combinations of multiple MAbs may provide the most effective form of passive immunotherapy, with the caveat that these may demonstrate emergent properties with regard to protective efficacy.

Original languageEnglish (US)
Pages (from-to)1880-1888
Number of pages9
JournalInfection and Immunity
Volume81
Issue number6
DOIs
StatePublished - Jun 2013

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Monoclonal Antibodies
Bacillus anthracis
Toxemia
Passive Immunization
anthrax toxin
Inbred C57BL Mouse
Immunoglobulin M
Immunoglobulin G
Macrophages
Antigens
Therapeutics
Infection
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays. / Pohl, Mary Ann; Rivera, Johanna; Nakouzi, Antonio; Chow, Siu Kei; Casadevall, Arturo.

In: Infection and Immunity, Vol. 81, No. 6, 06.2013, p. 1880-1888.

Research output: Contribution to journalArticle

Pohl, Mary Ann ; Rivera, Johanna ; Nakouzi, Antonio ; Chow, Siu Kei ; Casadevall, Arturo. / Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays. In: Infection and Immunity. 2013 ; Vol. 81, No. 6. pp. 1880-1888.
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