Mechanisms and Applications of Antiviral Neutralizing Antibodies - Creative Biolabs
The document provides an overview of neutralizing antibodies, which are critical in identifying and neutralizing pathogens, particularly viruses. It details their mechanisms of action, types, and clinical applications, including the potential of HIV and SARS-CoV-2 neutralizing antibodies in prevention and treatment. Challenges in developing these antibodies include viral mutation, manufacturing costs, and the need for specificity.
Introduction to Antibodies
1
Whatare 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
Antibodiesare Y-shaped proteins produced by the immune system to identify and
neutralize pathogens like viruses and bacteria.
Antibodies combat pathogens through several mechanisms
1. Recognition and Binding: They identify and attach to specific
antigens on pathogens.
2. Neutralization: They block pathogens from infecting cells or
interacting with their targets.
3. Opsonization: They coat pathogens, enhancing their uptake
and destruction by phagocytes.
4. Activation of the Complement System: They trigger a
cascade that leads to the destruction of pathogens.
5. Cell-Mediated Cytotoxicity: They recruit immune cells like
natural killer cells to destroy infected or transformed cells.
4.
What are NeutralizingAntibodies?
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 Regulationof Neutralizing Antibodies
The production of virus-neutralizing antibodies is a sophisticated immune
process, facilitated by the interaction of various immune cells and molecules.
1. Antigen Recognition and Capture
2. T Cell Activation
3. B Cell Activation and Differentiation
4. Plasma Cell Differentiation
5. Antibody Production and Secretion
• Helper T Cells (CD4+ T Cells)
• Antigen Presentation
• Regulatory T Cells (Tregs)
• BCR Affinity
Regulatory factors
6.
Mechanism of Action
Neutralizingantibodies 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 NeutralizationIn Vitro
A. Prevent virus attachment to host cell receptors by
degrading or altering the configuration of the viral spike
protein.
B. Cluster virus particles to hinder attachment to host cell
receptors.
C. Directly block the binding of the viral spike protein to host
cell receptors through steric hindrance.
D. Block the fusion of the virus and host cell membranes
through spatial obstruction.
E. Prevent conformational changes in the spike protein
required for viral entry into host cells.
F. For viruses that enter endosomes, prevent entry into the
cytoplasm by blocking endosomal escape and/or binding
to endosomal receptors.
G. Prevent the virus from escaping from the cells.
Mechanisms of neutralization in vitro. (Burton, et al, 2023)
8.
Types of NeutralizingAntibodies
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 antibodysite
(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 NeutralizingAntibody
- 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 NeutralizingAntibody 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