Virus Neutralization by Antibodies

Neutralizing Antibodies

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. NAbs are an important specific defense against viral invaders. A NAb might block interactions with the receptor, or might bind to glycoproteins of enveloped viruses or capsid proteins of non-enveloped viruses. Furthermore, NAb can act by preventing particles from undergoing structural changes often needed for successful cell entry. Only a small subset of the many antibodies that bind a virus is capable of neutralization. They are markers of immunity against reinfection after the acute infection has been cleared. Such immunity can be lifelong. However, it is not surprising that some viruses have developed mechanisms to avoid antibody-mediated neutralization.

Fig.1 Neutralization of viruses by functions of the IgG Fab fragment. (Arvin, 2020)

NAb vs Non-NAb

Based on the mechanisms of action, antiviral antibodies can be categorized into NAbs and non-NAbs. NAbs are an essential part of the human immune response that involves an intricate relationship between the innate and adaptive immune systems to prevent infection. Non-NAbs also recognize and attach to dangerous invaders, but they cannot prevent it from spreading. There is general agreement that NAbs act by binding to a specific epitope on the viral envelope and lead to neutralization or show antiviral activity. Non-NAb antibodies may not bind to the right region. Non-NAbs are helpful because macrophages use them as tethers to engulf and degrade the virus, but they’re not as powerful for fighting infections as neutralizing antibodies. In some cases, the binding of viruses to non-neutralizing antibodies may cause Antibody-Dependent Enhancement (ADE), which enhances viruses entry into host cells, and sometimes also its replication.

Fig.2 Potential mechanisms of coronavirus antibody neutralization and antibody enhancement of infection. (Abraham, 2020)

Mechanisms of Virus Neutralization

Neutralization of infectivity is thought to be the main mechanism of protection by antibodies and many mechanisms for neutralization have been proposed. The mechanism of neutralization refers specifically to which early step in the viral replicative cycle is blocked. Neutralization by antibody can be mediated by: aggregation of virions, destabilization of the virion structure, inhibition of virion attachment to target cells, inhibition of the fusion of the virion lipid membrane with the membrane of the host cell, inhibition of the entry of the genome of non-enveloped viruses into the cell cytoplasm, inhibition of a function of the virion core through a signal transduced by an antibody, transcytosing IgA, and binding to nascent virions to block their budding or release from the cell surface.

Fig.3 An overview of the mechanisms through which antibodies neutralize virus infectivity. (Reading, 2007)

The neutralization assay is a powerful technique to determine the inhibitory effect of antibodies of small molecules directly on the virus. Scientists at Creative Biolabs serve neutralization tests to determine the effectiveness of antibody treatments.

Our neutralization assays include

• ELISA-Based Receptor-Binding Inhibition Assay
• FC-Based Receptor-Binding Inhibition Assay
• Pseudovirus Neutralization Assay

Please feel free to contact us for further information.

References

1. Arvin, A.M.; et al. A perspective on the potential antibody-dependent enhancement of SARS-CoV-2. Nature. 2020, 584 (7821): 353-363.
2. Abraham, J. Passive antibody therapy in COVID-19. Nature Reviews Immunology. 2020, 20 (7): 401-403.
3. Reading, S.A.; Dimmock, N.J. Neutralization of animal virus infectivity by antibody. Archives of virology. 2007, 152 (6): 1047-1059.

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