サポート ブログ Monoclonal Antibodies in the Fight Against AMR

Monoclonal Antibodies in the Fight Against AMR

Biointron 2024-01-25 Read time: 4 mins
AMR.jpg
Timeline of mAb technologies related to AMR. DOI: 10.3389/fmicb.2022.1080059

Antimicrobial resistance (AMR) is a major threat to human health around the globe. It occurs when microorganisms, such as bacteria, viruses, parasites, or fungi, evolve mechanisms to withstand the effects of antimicrobial drugs. Overuse and misuse of antibiotics in both human and animal settings have accelerated the development of resistant strains, creating a pressing need for novel therapeutic approaches.1

Monoclonal antibodies (mAbs) are immunoglobulins derived from a monoclonal cell line and with a defined specificity and made in a lab. Unlike traditional antibiotics that directly attack bacteria, mAbs target specific proteins on the surface of pathogens, disrupting their ability to cause infection. However, while mAbs have been successful in treating human viral pathogens such as respiratory syncytial virus (RSV), Influenza and SARS-CoV-2, only three FDA-approved antibody therapies for bacterial infections exist, with the rest in clinical trials.

Challenges include the significance of Fc effector functions in bacterial clearance and killing, and the difficulty in finding the most suitable antigen when bacteria expose hundreds of antigens on their surface. Furthermore, certain bacteria can form tough biofilms and dwell in parts of the body with limited mAb distribution. Nonetheless, advancements in the field of antibody development are producing hopeful results, particularly from artificial intelligence, computational design, hinge region engineering, nucleic acid-encoded mAbs, and hetero-oligomerization.2

A computational approach is the design of modular nanocages, which are based on the idea that the assembly of particular antibodies can recognize a larger target compared to a single antibody. Divine et al. (2021) described a method to increase antibody valency through antibody-based protein nanoparticles for IgG antibodies, composed of an Fc fusion or antibody/homo-oligomer that controls Fc-binding and nanocage assembly.3

Currently, several clinical studies are being carried out for antibodies against bacterial toxins, surface proteins, and polysaccharides. Each target has its own pros and cons as anti-bacterial targets, with initial efforts focusing on toxin neutralization, as mAb therapies were thought to be able to inhibit virulence, without creating selective pressures on the organism.4 For example, suvratoxumab, a fully human, half-life extended IgG1 mAb targeting S. aureus alpha toxin, is being evaluated as a pre-emptive treatment for ventilator associated pneumonia.5


At Biointron, we are dedicated to accelerating your antibody discovery, optimization, and production needs. Our team of experts can provide customized solutions that meet your specific research needs. Contact us to learn more about our services and how we can help accelerate your research and drug development projects. 


References:

  1. Murray, C. J., Ikuta, K. S., Sharara, F., Swetschinski, L., Robles Aguilar, G., Gray, A., Han, C., Bisignano, C., Rao, P., Wool, E., Johnson, S. C., Browne, A. J., Chipeta, M. G., Fell, F., Hackett, S., Haines-Woodhouse, G., Kashef Hamadani, B. H., Kumaran, E. A. P., McManigal, B., … Naghavi, M. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet, 399(10325), 629–655. https://doi.org/10.1016/S0140-6736(21)02724-0

  2. Troisi, M., Marini, E., Abbiento, V., Stazzoni, S., Andreano, E., & Rappuoli, R. (2022). A new dawn for monoclonal antibodies against antimicrobial resistant bacteria. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.1080059

  3. Divine, R., Dang, H. V., Ueda, G., Fallas, J. A., Vulovic, I., Sheffler, W., Saini, S., Zhao, Y. T., Raj, I. X., Morawski, P. A., Jennewein, M. F., Homad, L. J., Wan, H., Tooley, M. R., Seeger, F., Etemadi, A., Fahning, M. L., Lazarovits, J., Roederer, A., . . . Baker, D. (2021). Designed proteins assemble antibodies into modular nanocages. Science (New York, N.Y.), 372(6537). https://doi.org/10.1126/science.abd9994

  4. Motley, M. P., Banerjee, K., & Fries, B. C. (2019). Monoclonal Antibody-Based Therapies for Bacterial Infections. Current Opinion in Infectious Diseases, 32(3), 210. https://doi.org/10.1097/QCO.0000000000000539

  5. François, B., Jafri, H. S., Chastre, J., Sánchez-García, M., Eggimann, P., Dequin, P. F., Huberlant, V., Viña Soria, L., Boulain, T., Bretonnière, C., Pugin, J., Trenado, J., Hernandez Padilla, A. C., Ali, O., Shoemaker, K., Ren, P., Coenjaerts, F. E., Ruzin, A., Barraud, O., … Maggiorini, M. (2021). Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial. The Lancet Infectious Diseases, 21(9), 1313–1323. https://doi.org/10.1016/S1473-3099(20)30995-6


Subscribe to our ブログ

Recent ブログ

The therapeutic efficacy of antibodies is closely related to their ability to recognize and bind specific epitopes on target antigens. Epitopes, or antigenic determinants, are a group of amino acids or other chemical groups that are part of a molecule to which an antibody attaches itself. Epitope characterization can help reveal the mechanism of antibody binding and apply intellectual property (patent) protection for novel antibodies, in addition to designing antibodies with high specificity and minimal cross-reactivity.

Jul 12, 2024
ブログ

Understanding the differences between antibody specificity and selectivity is essential for designing and interpreting antibody-based assays in research for experimental accuracy and data interpretation. Antibody specificity refers to an antibody's ability to recognize and bind to a particular epitope—a unique part of an antigen that elicits an immune response.

Jul 10, 2024
ブログ

Antibody-based assays are essential tools in biomedical research, providing the means to detect, quantify, and visualize specific proteins or antigens within complex biological samples. These assays' efficacy hinges on the antibodies' precise properties. While affinity, avidity, specificity, and selectivity are fundamental to antibody performance, the ultimate impact of these properties is heavily influenced by the experimental context in which the antibody is employed.

Jul 08, 2024
ブログ

Biologics, particularly antibodies, have become indispensable in biomedical research and therapeutic development. Research-use-only (RUO) biologics play a pivotal role in preclinical studies, providing researchers with the necessary tools to explore antibody functions and therapeutic potential in vivo.

Jul 04, 2024
ブログ

お客様の利便性を向上させるためにクッキーを使用しています。詳しくは プライバシーポリシー をご覧ください。