rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis

• Published in: Frontiers in microbiology Vol. 13; p. 960937
• Main Authors: Derkaev, Artem A., Ryabova, Ekaterina I., Esmagambetov, Ilias B., Shcheblyakov, Dmitry V., Godakova, Svetlana A., Vinogradova, Irina D., Noskov, Anatoly N., Logunov, Denis Y., Naroditsky, Boris S., Gintsburg, Alexander L.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 27.09.2022
• Subjects: adeno-associated viral vector (AAV); botulinum neurotoxin; botulism; Clostridium botulinum; Microbiology; single-domain antibodies; VHH
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2022.960937

Botulinum neurotoxin (BoNT) is one of the most dangerous bacterial toxins and a potential biological weapon component. BoNT mechanism of pathological action is based on inhibiting the release of neurotransmitters from nerve endings. To date, anti-BoNT therapy is reduced to the use of horse hyperimmune serum, which causes many side effects, as well as FDA-approved drug BabyBig which consists of human-derived anti-BoNT antibodies (IgG) for infant botulinum treatment. Therapeutics for botulism treatment based on safer monoclonal antibodies are undergoing clinical trials. In addition, agents have been developed for the specific prevention of botulism, but their effectiveness has not been proved. In this work, we have obtained a recombinant adeno-associated virus (rAAV-B11-Fc) expressing a single-domain antibody fused to the human IgG Fc-fragment (B11-Fc) and specific to botulinum toxin type A (BoNT/A). We have demonstrated that B11-Fc antibody, expressed via rAAV-B11-Fc treatment, can protect animals from lethal doses of botulinum toxin type A, starting from day 3 and at least 120 days after administration. Thus, our results showed that rAAV-B11-Fc can provide long-term expression of B11-Fc-neutralizing antibody in vivo and provide long-term protection against BoNT/A intoxication. Consequently, our study demonstrates the applicability of rAAV expressing protective antibodies for the prevention of intoxication caused by botulinum toxins.