Characterization of serum anti-diphtheria antibody activity following administration of equine anti-toxin for suspected diphtheria

Heidi L Smith; Greg Saia; Maria Lobikin; Tejpratap Tiwari; Su-Chun Cheng; Deborah C Molrine

doi:10.1080/21645515.2017.1362516

Characterization of serum anti-diphtheria antibody activity following administration of equine anti-toxin for suspected diphtheria

Hum Vaccin Immunother. 2017 Nov 2;13(11):2738-2741. doi: 10.1080/21645515.2017.1362516. Epub 2017 Sep 21.

Authors

Heidi L Smith¹, Greg Saia², Maria Lobikin³, Tejpratap Tiwari⁴, Su-Chun Cheng⁵, Deborah C Molrine⁶

Affiliations

¹ a MassBiologics of the University of Massachusetts Medical School , Boston , MA , USA.
² b MassBiologics of the University of Massachusetts Medical School , Boston , MA , USA.
³ c MassBiologics of the University of Massachusetts Medical School , Boston , MA , USA.
⁴ d Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases , Centers for Disease Control and Prevention , Atlanta , GA , USA.
⁵ e Department of Biostatistics and Computational Biology , Dana Farber Cancer Institute , Boston , MA , USA.
⁶ f MassBiologics of the University of Massachusetts Medical School , Boston , MA , USA.

Abstract

There is a global shortage of equine-derived diphtheria anti-toxin (DAT) for diphtheria treatment. There are few existing data on serum antibody concentrations and neutralizing activity post-treatment to support development of new therapeutics. Antibody concentrations were quantified by ELISA and anti-toxin neutralizing activity by cytotoxicity assay in serum from 4 patients receiving DAT for suspected diphtheria. Using linear mixed effects modeling, estimated mean (SE) half-life was 78.2 (20.0) hours. Maximum serum neutralizing activity ranged from 28.42-38.64 AU/mL with an estimated mean AUC_1-72 of 1396.7 (399.3) AU/mL*hr. These data provide a standard of comparison for development of novel anti-toxins to replace DAT.

Keywords: anti-toxin; diphtheria; pharmacokinetics; toxin neutralizing activity.

MeSH terms

Administration, Intravenous
Adult
Aged
Animals
Antibodies, Anti-Idiotypic / biosynthesis
Antibodies, Anti-Idiotypic / blood*
Antibodies, Bacterial / administration & dosage
Antibodies, Bacterial / immunology*
Antibodies, Bacterial / metabolism
Antibodies, Bacterial / therapeutic use
Chlorocebus aethiops
Cytotoxicity Tests, Immunologic
Diphtheria / blood
Diphtheria / immunology
Diphtheria / therapy*
Diphtheria Antitoxin / administration & dosage
Diphtheria Antitoxin / immunology*
Diphtheria Antitoxin / metabolism
Diphtheria Antitoxin / therapeutic use
Enzyme-Linked Immunosorbent Assay
Female
Half-Life
Horses
Humans
Male
Middle Aged
Neutralization Tests
Vero Cells

Substances

Antibodies, Anti-Idiotypic
Antibodies, Bacterial
Diphtheria Antitoxin