Mechanisms and Applications of Antiviral Neutralizing Antibodies - Creative Biolabs

Neutralizing antibodies, pivotal in immune defense, specifically bind and inhibit viral pathogens, thereby playing a crucial role in protecting against and mitigating infectious diseases. In this slide, we will introduce what antibodies and neutralizing antibodies are, the production and regulation of neutralizing antibodies, their mechanisms of action, classification and applications, as well as the challenges they face.

1. Mechanisms and Applications of Antiviral Neutralizing Antibodies Tel: [phone] Email: [email protected] SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA

2. Introduction to Antibodies 1 What are Neutralizing Antibodies? 2 Production and regulation of neutralizing antibodies 3 Mechanism of Action 4 Contents Types of Neutralizing Antibodies 5 Application of neutralizing antibody 6 Challenges in Neutralizing Antibody Response 7 Viral Antibody Service 8

3. Introduction to Antibodies Antibodies are Y-shaped proteins produced by the immune system to identify and neutralize pathogens like viruses and bacteria. Antibodies combat pathogens through several mechanisms Recognition and Binding: They identify and attach to specific antigens on pathogens. Neutralization: They block pathogens from infecting cells or interacting with their targets. Opsonization: They coat pathogens, enhancing their uptake and destruction by phagocytes. Activation of the Complement System: They trigger a cascade that leads to the destruction of pathogens. Cell-Mediated Cytotoxicity: They recruit immune cells like natural killer cells to destroy infected or transformed cells.

4. What are Neutralizing Antibodies? Antibodies are Y-shaped proteins produced by the immune system to identify and neutralize pathogens like viruses and bacteria. Distinction between neutralizing and non-neutralizing antibodies Only neutralizing antibodies can deactivate the virus, allowing it to be engulfed by cells. While non-neutralizing antibodies also bind to pathogens, they do not block infection directly. Instead, they might tag the pathogen for destruction by other immune cells, facilitate the removal of the pathogen through phagocytosis, or trigger other immune responses that contribute to the pathogen's clearance from the body.

5. Production and Regulation of Neutralizing Antibodies The production of virus-neutralizing antibodies is a sophisticated immune process, facilitated by the interaction of various immune cells and molecules. Antigen Recognition and Capture T Cell Activation B Cell Activation and Differentiation Plasma Cell Differentiation Antibody Production and Secretion Helper T Cells (CD4+ T Cells) Antigen Presentation Regulatory T Cells (Tregs) BCR Affinity Regulatory factors

6. Mechanism of Action Neutralizing antibodies are a specific type of antibody that play a crucial role in defending against viral infections: Binding to Viruses : Neutralizing antibodies recognize and bind specifically to antigens on the surface of a virus. Blocking Virus Entry : By binding to these surface proteins, neutralizing antibodies can block the virus from attaching to and entering host cells. Preventing Viral Replication : Once a virus is blocked from entering a cell, it cannot replicate. Tagging for Destruction : Besides blocking viruses, neutralizing antibodies can also tag them for destruction. Triggering Immune Responses : Neutralizing antibodies can activate other parts of the immune system, such as the complement system.

7. Mechanisms of Neutralization In Vitro Prevent virus attachment to host cell receptors by degrading or altering the configuration of the viral spike protein. Cluster virus particles to hinder attachment to host cell receptors. Directly block the binding of the viral spike protein to host cell receptors through steric hindrance. Block the fusion of the virus and host cell membranes through spatial obstruction. Prevent conformational changes in the spike protein required for viral entry into host cells. For viruses that enter endosomes, prevent entry into the cytoplasm by blocking endosomal escape and/or binding to endosomal receptors. Prevent the virus from escaping from the cells. Mechanisms of neutralization in vitro. (Burton, et al, 2023)

8. Types of Neutralizing Antibodies Virus-Specific Neutralizing Antibodies Influenza-Specific Antibodies: Target hemagglutinin and neuraminidase on the influenza virus, blocking entry and release from host cells. HIV-Specific Antibodies: Bind to the gp120 or gp41 envelope proteins of HIV, preventing the virus from binding to the CD4 receptor and co-receptors on T-cells. SARS-CoV-2 Antibodies: Target the spike protein, particularly the receptor-binding domain that attaches to the ACE2 receptor on human cells, blocking entry. Toxin-Neutralizing Antibodies (Antitoxins) These antibodies neutralize the effects of bacterial toxins. For example, tetanus or diphtheria antitoxins neutralize toxins released by the respective bacteria, preventing toxin-mediated damage. Therapeutic Neutralizing Antibodies Monoclonal Antibodies: Engineered in laboratories to target specific antigens. Polyclonal Antibodies: These are collections of antibodies that target multiple epitopes or antigens.

9. HIV neutralizing antibody site ( Stefic , et al.) Mechanism of Action HIV neutralizing antibodies primarily target the envelope glycoproteins on the surface of the virus, specifically gp120 and gp41. Binding to gp120: Neutralizing antibodies can bind to the gp120 glycoprotein, blocking its interaction with the CD4 receptor. Preventing Fusion: Some neutralizing antibodies target gp41, the glycoprotein involved in the fusion of the viral membrane with the host cell membrane. Clinical Implications and Therapeutic Potential HIV neutralizing antibodies primarily target the envelope glycoproteins on the surface of the virus, specifically gp120 and gp41. Prevention: HIV neutralizing antibodies have great potential in preventive strategies. Therapeutic Treatment: In therapeutic contexts, HIV neutralizing antibodies can be administered to individuals already infected with HIV to help control viral replication and reduce viral load. Application of Neutralizing Antibody - SARS-CoV-2 Neutralizing Antibodies

10. Application of Neutralizing Antibody - SARS-CoV-2 Neutralizing Antibodies Mechanism of Action Blockade of Viral Entry: By binding to the receptor-binding domain (RBD) of the spike protein, these antibodies block the virus's entry mechanism. Prevention of Membrane Fusion: Some antibodies can prevent the conformational changes in the spike protein that are necessary for the virus to fuse with the host cell membrane. Clinical Implications and Therapeutic Potential Prevention: Neutralizing antibodies are key in preventing the progression of COVID-19 to more severe forms. Therapeutic Treatment: In therapeutic contexts, HIV neutralizing antibodies can be administered to individuals already infected with HIV to help control viral replication and reduce viral load. Development of SARS-CoV-2 neutralizing antibodies ( Gruell , et al. )

11. Challenges in Neutralizing Antibody Response Variability and Mutation Pathogens, especially viruses, can rapidly mutate. This variability can alter epitopes (the part of the antigen to which antibodies bind), potentially reducing the effectiveness of existing neutralizing antibodies. It is crucial for neutralizing antibodies to be highly specific to their target antigens without cross-reacting with other non-target molecules. Cost The development and production of monoclonal antibodies can be costly. Producing neutralizing antibodies at a scale sufficient for widespread clinical use presents significant logistical and technical challenges. Selectivity and Specificity Manufacturing Scalability

12. Creative-Biolabs--Viral Antibody Service Virus Neutralizing Antibody Development Services Cytopathic Effect (CPE) Assay ELISA-based Receptor-Binding Inhibition Assay FC-based Receptor-Binding Inhibition Assay Pseudovirus-based Neutralization Assay Determination of Neutralizing Antibody Titer Virus Antibodies Secondary Antibodies lsotype Controls Virus Detection Probe Virus Vaccine Serum Pseudovirus Virology Testing Plaque Assay TCID50 Assay Antibody-Dependent Enhancement (ADE) Assay Microneutralization Assay Hemagglutination Inhibition Assay Comprehensive Virus Research Products

13. Mechanisms and Applications of Antiviral Neutralizing Antibodies Email: [email protected] SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA