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Neutralisation or neutralization or sterilizing immunity in the immunological sense refers to the ability of specific antibodies to block the site(s) on viruses that the latter use to enter target cells. Neutralisation renders the virus no longer infectious (or pathogenic). The surface of viruses contains viral proteins that bind to host cell receptors enabling infection of the host cell. Neutralizing antibodies bind and block the viral surface proteins, preventing host cell entry. After a first encounter by vaccination or natural infection, immunological memory allows for a more rapid production of neutralizing antibodies following the next exposure to the virus.

Vaccines

Vaccines are utilized to develop immunity to a virus. An effective vaccine induces the production of antibodies that are able to neutralize the majority of variants of a virus, although virus mutation may cause the need for continuous vaccination. Introducing a weakened form of a virus through vaccination allows for the production of neutralizing antibodies by B cells. After a second exposure, the neutralizing antibody response is more rapid due to the existence of memory B cells that produce antibodies specific to the virus.

Viral infection and antibody response

Viruses cause infection by entering cells and taking over cellular machinery in order to produce copies of themselves(8). Cell entry is essential in the viral life cycle, as viruses cannot replicate outside of cells and depend on the use of internal components of host cells for replication. Both enveloped and non-enveloped viruses require interaction between viral proteins and cell membrane receptors in order to gain entry into the target cell(7). Once attached to the cell surface, enveloped and non-enveloped viruses can use a variety of mechanisms for entry. Enveloped viruses have a viral envelope, or outer lipid bilayer membrane that is generated by budding from the virus producer cell; these viruses enter cells when this membrane fuses with the target cell membrane(8). Non-enveloped viruses can enter cells by forming pores or other breakdowns in integrity of the plasma membrane(7). Once viruses have entered the cell, they then use a variety of mechanisms to hijack cellular materials and functions to produce viral proteins.  

Antibody production is a critical part of the vertebrate immune response to foreign invaders. Antibodies are proteins that can recognize and bind to specific viral antigens. In B cells, somatic recombination can generate a vast repertoire of different antibodies, each produced by a different B (or plasma) cell – so that a vast array of antigens can be neutralized. Neutralizing antibodies can block at multiple points in a viral entry pathway(5). Blocking access to cell surface receptors is a common strategy and is often mediated by binding to and neutralizing glycoproteins of enveloped viruses and the protein shell of non-enveloped viruses (9). Neutralizing antibodies can block infection post-attachment as well. For example, neutralizing antibodies can prevent conformational changes in a viral protein that is required for the virus to enter the cell after attachment to has occurred. In some cases, the virus is unable to infect even after the antibody dissociates.

Virus evasion of neutralizing antibodies

Viruses use a variety of mechanisms to evade neutralizing antibodies (9). Viral genomes mutate at a high rate. Mutations that allow viruses to evade a neutralizing antibody will be selected for, and hence prevail. Conversely, antibodies also simultaneously evolve by affinity maturation during the course of an immune response, thereby improving recognition of viral particles. Some viruses evolve faster than others, which can require the need for vaccines to be updated in response. This is most exemplified by the vaccine for the influenza virus, which must be updated annually to account for the recent circulating strains of the virus. Conserved parts of viral proteins that play a central role in viral function are less likely to evolve over time, and therefore are more vulnerable to antibody binding. However, viruses have evolved certain mechanisms to steric access of an antibody to these regions, making binding difficult. Viruses with a low density of surface structural proteins are more difficult for antibodies to bind to. “Glycan shields” can also facilitate evasion of neutralizing antibodies. That is, the presence of N- and O- linked glycans may decrease antibody binding affinity to some viral glycoproteins. HIV-1, the cause of human AIDS, uses both of these mechanisms.

Treatment with neutralizing antibodies

Broadly neutralizing antibodies (bNAbs) have been researched as a potential treatment for HIV-1 and influenza (2,4). bNAbs are antibodies that can bind to and block many variants of a virus, and therefore have a heightened efficacy (10). In the past ten years, much effort has been directed at identifying and testing bNAbs against HIV-1 (6).