Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

Area of Science:

• Biochemistry
• Immunology
• Toxicology

Background:

• Botulinum neurotoxins (BoNTs) are highly toxic substances causing botulism and are classified as bioweapons.
• Human-neutralizing antibodies are crucial for countering BoNT threats and natural botulism.
• Previous macaque-derived scFv-Fc ELC18 showed neutralizing potential against BoNT/E.

Purpose of the Study:

• To develop a humanized antibody with increased immunotolerance for neutralizing BoNT/E.
• To evaluate the protective and prophylactic efficacy of the humanized antibody hu8ELC18 against BoNT/E in a mouse model.

Main Methods:

• Germline humanization of macaque-derived scFv-Fc ELC18 into a full IgG (hu8ELC18).
• Assessment of protection against BoNT/E using mouse protection and paralysis assays.
• Evaluation of prophylactic capacity by administering hu8ELC18 prior to BoNT/E exposure.

Main Results:

• A concentration of 2.5 ng/mouse of hu8ELC18 protected against 5 mouse lethal doses (MLD) of BoNT/E.
• Complete neutralization of 1 LD50 of BoNT/E was achieved with 8 ng of hu8ELC18.
• hu8ELC18 provided protection from 5 MLD when injected up to 14 days before BoNT/E administration.

Conclusions:

• The humanized IgG hu8ELC18 demonstrates significant protective and prophylactic efficacy against BoNT/E in vivo.
• hu8ELC18 is expected to have high tolerance in humans, offering a potential therapeutic strategy against botulism.