A neutralizing antibody (NAb) is an
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
that defends a
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
from a
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic.
Neutralizing antibodies are part of the
humoral
Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it invo ...
response of the
adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
against
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es,
intracellular bacteria
Intracellular bacteria are bacteria, which have the capability to enter and survive within the cells of the host organism. Many of them are capable of growth extracellularly, but some of them can grow and reproduce only intracellularly (obligate i ...
and
microbial toxin
Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. ...
. By binding specifically to surface structures (
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its
host cells
In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...
it might infect and destroy.
Mechanism
![NAb esquema](https://upload.wikimedia.org/wikipedia/commons/4/44/NAb_esquema.jpg)
In order to enter cells, pathogens, such as circulating viral particles or extracellular bacteria, use molecules on their surfaces to interact with the
cell surface receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...
s of their target cell which allows them to enter the cell and start their
replication cycle.
Neutralizing antibodies can inhibit infectivity by binding to the pathogen and blocking the molecules needed for cell entry. This can be due to the antibodies statically interfering with the pathogens, or toxins attaching to host cell receptors. In case of a viral infection, NAbs can bind to glycoproteins of
enveloped viruses or
capsid proteins
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
of non-enveloped viruses.
Furthermore, neutralizing antibodies can act by preventing particles from undergoing structural changes often needed for successful cell entry. For example, neutralizing antibodies can prevent
conformational change
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...
s of viral proteins that mediate the membrane fusion needed for entry into the host cell.
In some cases, the virus is unable to infect even after the antibody dissociates. The pathogen-antibody complex is eventually taken up and degraded by macrophages.
Neutralizing antibodies are also important in neutralizing the toxic effects of bacterial toxins. An example of a neutralizing antibody is
diphtheria antitoxin
Diphtheria antitoxin (DAT) is a medication made up of antibodies used in the treatment of diphtheria. It is no longer recommended for prevention of diphtheria. It is given by injection into a vein or muscle.
Side effects are common. They inclu ...
, which can neutralize the biological effects of
diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
.
Neutralizing antibodies are not effective against extracellular bacteria, as the binding of antibodies does not prevent bacteria from replicating. Here, the immune system uses other
functions of antibodies, like
opsonisation
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...
and
complement
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
activation, to kill the bacteria.
Difference between neutralizing antibodies and binding antibodies
Not all antibodies that bind to a pathogenic particle are neutralizing. Non-neutralizing antibodies, or binding antibodies, bind specifically to the pathogen, but do not interfere with their infectivity. That might be because they do not bind to the right region. Non-neutralizing antibodies can be important to flag the particle for
immune cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, signaling that it has been targeted, after which the particle is processed and consequently destroyed by recruited immune cells.
Neutralizing antibodies on the other hand can neutralize the biological effects of the antigen without a need for immune cells.
In some cases, non-neutralizing antibodies, or an insufficient amount of neutralizing antibodies binding to viral particles, can be utilized by some species of virus to facilitate uptake into their host cells. This mechanism is known as
antibody-dependent enhancement
Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replic ...
.
It has been observed for
Dengue virus
''Dengue virus'' (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family ''Flaviviridae''; genus ''Flavivirus''. Four serotypes of the virus have been found, a reported fifth has yet to be co ...
and
Zika virus
''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...
.
Production
Antibodies are produced and secreted by
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s.
When B cells are produced in the
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
, the genes that encode the antibodies undergo random
genetic recombination
Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryo ...
(
V(D)J recombination
V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell rece ...
), which results in every mature B cell producing antibodies that differ in their
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sequence in the
antigen-binding region. Therefore, every B cell produces antibodies that bind specifically to different
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s.
A strong diversity in the antibody repertoire allows the immune system to recognize a plethora of pathogens which can come in all different forms and sizes. During an infection only antibodies that bind to the pathogenic antigen with high affinity are produced. This is achieved by
clonal selection
In immunology, clonal selection theory explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an ...
of a single B cell clone: B cells are recruited to the site of infection by sensing
interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...
s that are released by the infected cells as part of the
innate immune response
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
. B cells display
B-cell receptor
The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...
s on their cell surface, which is just the antibody anchored to the cell membrane. When the B-cell receptor binds to its cognate antigen with high affinity, an intracellular
signalling cascade
A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...
is triggered. In addition to binding to an antigen, B cells need to be stimulated by
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s produced by
T helper cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
s as part of the
cellular
Cellular may refer to:
*Cellular automaton, a model in discrete mathematics
* Cell biology, the evaluation of cells work and more
* ''Cellular'' (film), a 2004 movie
*Cellular frequencies, assigned to networks operating in cellular RF bands
*Cell ...
response of the immune system against the pathogen. Once a B cell is fully activated, it rapidly proliferates and differentiates into
plasma cell
Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...
s. Plasma cells then secrete the antigen-specific antibody in large quantities.
After a first encounter of the antigen by vaccination or natural infection,
immunological memory
Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...
allows for a more rapid production of neutralizing antibodies following the next exposure to the virus.
Virus evasion of neutralizing antibodies
Viruses use a variety of mechanisms to evade neutralizing antibodies.
Viral
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
s mutate at a high rate.
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s that allow viruses to evade a neutralizing antibody will be selected for, and hence prevail. Conversely, antibodies also simultaneously evolve by
affinity maturation
In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce ...
during the course of an immune response, thereby improving recognition of viral particles. 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 hinder
steric
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
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.
Some viral glycoproteins are heavily glycosylated by N- and O- linked
glycan
The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate p ...
s, creating a so-called glycan shield, which may decrease antibody binding affinity and facilitate evasion of neutralizing antibodies.
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey, ...
, the cause of human
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
, uses both of these mechanisms.
Medical uses of neutralizing antibodies
Neutralizing antibodies are used for
passive immunisation Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when h ...
, and can be used for patients even if they do not have a healthy immune system.
In the early 20th century, infected patients were injected with
antiserum
Antiserum is a blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous ...
, which is the
blood serum
Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not u ...
of a previously infected and recovered patient containing
polyclonal antibodies
Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against a ...
against the infectious agent. This showed that antibodies could be used as an effective treatment for viral infections and toxins.
Antiserum is a very crude therapy, because antibodies in the plasma are not purified or standardized and the blood plasma could be rejected by the donor.
As it relies on the donation from recovered patients it cannot be easily scaled up. However, serum therapy is today still used as the first line of defence during an outbreak as it can relatively quickly obtained.
Serum therapy was shown to reduce mortality in patients during the
2009 swine flu pandemic
The 2009 swine flu pandemic, caused by the H1N1 influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, is the third recent flu pandemic involving the H1N1 virus (the first being the 1918–1920 Span ...
and the
Western African Ebola virus epidemic
The 2013–2016 epidemic of Ebola virus disease, centered in Western Africa, was the most widespread outbreak of the disease in history. It caused major loss of life and socioeconomic disruption in the region, mainly in Guinea, Liberia and S ...
.
It is also being tested as possible treatment for
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
.
Immunoglobulin therapy
Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory de ...
, which uses a mixture of antibodies obtained from healthy people, is given to
immunodeficient
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
or
immunosuppressed
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
patients to fight off infections.
For a more specific and robust treatment, purified
polyclonal
Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of ...
or
monoclonal antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ca ...
(mAb) can be used. Polyclonal antibodies are collection of antibodies that target the same pathogen but bind to different
epitopes
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
. Polyclonal antibodies are obtained from human donors or animals that have been exposed to the antigen. The antigen injected into the animal donors can be designed in such a way to preferably produce neutralizing antibodies.
Polyclonal antibodies have been used as treatment for
cytomegalovirus
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
(CMV),
hepatitis b virus
''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus ''Orthohepadnavirus'' and a member of the ''Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B.
Disease
Despite there bein ...
(HBV),
rabies virus
Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
,
measles virus
''Measles morbillivirus'' (MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus ''Morbillivirus'' within the family ''Paramyxoviridae''. It is the cause of measles. Human ...
, and
respiratory syncytial virus
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
(RSV).
Diphtheria antitoxin
Diphtheria antitoxin (DAT) is a medication made up of antibodies used in the treatment of diphtheria. It is no longer recommended for prevention of diphtheria. It is given by injection into a vein or muscle.
Side effects are common. They inclu ...
contains polyclonal antibodies against the
diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
.
By treating with antibodies binding multiple epitopes, the treatment is still effective even if the virus mutates and one of the epitopes changes in structure. However, because of the nature of the production, treatment with polyclonal antibodies has
batch to batch variation and low
antibody titer
Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
s.
Monoclonal antibodies, on the other hand, all bind the same epitope with high specificity. They can be produced with the
Hybridoma technology
Hybridoma technology is a method for producing large numbers of identical antibodies (also called monoclonal antibodies). This process starts by injecting a mouse (or other mammal) with an antigen that provokes an immune response. A type of white ...
, which allows the production of mAbs in large quantities.
mAbs against infections stop working when virus mutates the epitope that is targeted by the mAbs or multiple strain are circulating. Example of drugs that use monoclonal antibodies include
ZMapp
ZMapp is an experimental biopharmaceutical drug comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. Two of the three components were originally developed at the Public Health Agency of Canada ...
against Ebola
and
Palivizumab
Palivizumab, sold under the brand name Synagis, is a monoclonal antibody produced by recombinant DNA technology used to prevent severe disease caused by respiratory syncytial virus (RSV) infections. It is recommended for infants at high-risk for RS ...
against RSV.
Many mABs against other infections are in clinical trials.
Neutralizing antibodies also play a role in active immunisation by
vaccination
Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
. By understanding the binding sites and structure of neutralizing antibodies in a natural immune response a vaccine can be rationally designed such that it stimulates the immune system to produce neutralizing antibodies and not binding antibodies.
Introducing a weakened form of a virus through vaccination allows for the production of neutralizing antibodies by
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s. After a second exposure, the neutralizing antibody response is more rapid due to the existence of
memory B cell
In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescen ...
s that produce antibodies specific to the virus.
An effective vaccine induces the production of antibodies that are able to neutralize the majority of variants of a virus, although virus mutation resulting in antibody evasion may require vaccines to be updated in response.
Some viruses evolve faster than others, which can require the need for vaccines to be updated in response. A well known example is the vaccine for the
influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
virus, which must be updated annually to account for the recent circulating strains of the virus.
Neutralizing antibodies may also assist the treatment of
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
.
[
] Although this type of antibody has the ability to fight
retroviral
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
infections, in some cases it attacks
pharmaceuticals
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
administered to the body which would otherwise treat multiple sclerosis. Recombinant protein drugs, especially those derived from animals, are commonly targeted by neutralizing antibodies. A few examples are Rebif, Betaseron and Avonex.
Methods for detection and quantification of neutralizing antibodies
Neutralization assays are capable of being performed and measured in different ways, including the use of techniques such as
plaque reduction (which compares counts of virus plaques in control wells with those in inoculated cultures), microneutralization (which is performed in
microtiter plate
A microplate, also known as a microtiter plate (''Microtiter'' is a registered trademark in the United States, therefore it should not be used generically without attribution), microwell plate or multiwell, is a flat plate with multiple "wells" ...
s filled with small amounts of
sera), and
colorimetric assays (which depend on biomarkers indicating metabolic inhibition of the virus).
Broadly neutralizing antibodies
Most of the neutralizing antibodies produced by the immune system are very specific for a single virus strain due to affinity maturation by B cells.
Some pathogens with high genetic variability, such as HIV, constantly change their surface structure such that neutralizing antibodies with high specificity to the old strain can no longer bind to the new virus strain. This immune evasion strategy prevents the immune system from developing immunological memory against the pathogen.
Broadly neutralizing antibodies (bNAbs), on the other hand, have the special ability to bind and neutralize multiple strains of a virus species.
bNAbs have been initially found in HIV patients.
However, they are quite rare: an ''in situ'' screening study showed that only 1% of all patients develop bNAbs against HIV.
bNABs can neutralize a wide range of virus strains by binding to conserved regions of the virus surface proteins that are unable to mutate because they are functionally essential for the virus replication. Most binding sites of bNAbs against HIV are on HIV's exposed surface antigen, the envelope (Env) protein (a trimer composed of
gp120
Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from ...
and
gp41
Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required fo ...
subunits). These site include the CD4 binding site or the gp41-gp120 interface.
Los Alamos National Laboratory's HIV Databases is a comprehensive resource that has a wealth of information about HIV sequences, bNAbs, and more.
Additionally, bNAbs have been found for other viruses including influenza,
hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
,
dengue
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic ...
and
West Nile virus
West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...
.
Research
Preliminary research is conducted to identify and test bNAbs against HIV-1.
bNAbs are used in research to rationally design vaccines to stimulate production of bNAbs and immunity against viruses. No antigen that triggers bNAb production in animal models or humans is known.
See also
*
Blocking antibody A blocking antibody is an antibody that does not have a reaction when combined with an antigen, but prevents other antibodies from combining with that antigen. This function of blocking antibodies has had a variety of clinical and experimental uses. ...
*
Humoral immunity
Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it in ...
References
{{DEFAULTSORT:Neutralizing Antibody
Antibodies