Monoclonal antibodies and toxins--a perspective on function and isotype

Abstract

Antibody therapy remains the only effective treatment for toxin-mediated diseases. The development of hybridoma technology has allowed the isolation of monoclonal antibodies (mAbs) with high specificity and defined properties, and numerous mAbs have been purified and characterized for their protective efficacy against different toxins. This review summarizes the mAb studies for 6 toxins--Shiga toxin, pertussis toxin, anthrax toxin, ricin toxin, botulinum toxin, and Staphylococcal enterotoxin B (SEB)--and analyzes the prevalence of mAb functions and their isotypes. Here we show that most toxin-binding mAbs resulted from immunization are non-protective and that mAbs with potential therapeutic use are preferably characterized. Various common practices and caveats of protection studies are discussed, with the goal of providing insights for the design of future research on antibody-toxin interactions.

Keywords: animal model; antibody; clearance; disease enhancement; in vivo; isotype; neutralization; protection; therapeutics; vaccine.

Figure 1

Distribution of mAbs classified as protective, indifferent, or disease-enhancing. (A) mAb studies divided into two groups. Group A consists of studies that describe multiple categories of mAbs (among protective, indifferent, and disease-enhancing). Group B consists of studies that describe only a single category of mAbs. n = 97 studies; (B) Distribution of mAbs with different activities from Group A studies. n = 2559 mAbs from 54 studies; (C) Distribution of mAbs with different activities from Group B studies. n = 111 mAbs from 43 studies; (D) Distribution of studies on protective, indifferent, or disease-enhancing mAbs.

Figure 2

Chronological distribution of mAb studies for individual toxin.

Figure 3

Distribution of mAb isotypes. (A) Isotype distribution of protective mAbs. n = 222 mAbs from 67 studies; (B) Isotype distribution of indifferent mAbs. n = 252 mAbs from 30 studies; (C) Isotype distribution of disease-enhancing mAbs. n = 28 mAbs from 3 studies. Only mAbs with defined isotypes are counted.