Antigenic escape

Last updated

Antigenic escape, immune escape, immune evasion or escape mutation occurs when the immune system of a host, especially of a human being, is unable to respond to an infectious agent: the host's immune system is no longer able to recognize and eliminate a pathogen, such as a virus. This process can occur in a number of different ways of both a genetic and an environmental nature. [1] Such mechanisms include homologous recombination, and manipulation and resistance of the host's immune responses. [2]

Contents

Different antigens are able to escape through a variety of mechanisms. For example, the African trypanosome parasites are able to clear the host's antibodies, as well as resist lysis and inhibit parts of the innate immune response. [3] A bacterium, Bordetella pertussis , is able to escape the immune response by inhibiting neutrophils and macrophages from invading the infection site early on. [4] One cause of antigenic escape is that a pathogen's epitopes (the binding sites for immune cells) become too similar to a person's naturally occurring MHC-1 epitopes, resulting in the immune system becoming unable to distinguish the infection from self-cells.[ citation needed ]

Antigenic escape is not only crucial for the host's natural immune response, but also for the resistance against vaccinations. The problem of antigenic escape has greatly deterred the process of creating new vaccines. Because vaccines generally cover a small ratio of strains of one virus, the recombination of antigenic DNA that lead to diverse pathogens allows these invaders to resist even newly developed vaccinations. [5] Some antigens may even target pathways different from those the vaccine had originally intended to target. [4] Recent research on many vaccines, including the malaria vaccine, has focused on how to anticipate this diversity and create vaccinations that can cover a broader spectrum of antigenic variation. [5] On 12 May 2021, scientists reported to The United States Congress of the continuing threat of COVID-19 variants and COVID-19 escape mutations, such as the E484K virus mutation. [6]

Mechanisms of evasion

Helicobacter pylori and homologous recombination

The most common of antigenic escape mechanisms, homologous recombination, can be seen in a wide variety of bacterial pathogens, including Helicobacter pylori , a bacterium that infects the human stomach. While a host's homologous recombination can act as a defense mechanisms for fixing DNA double stranded breaks (DSBs), it can also create changes in antigenic DNA that can create new, unrecognizable proteins that allow the antigen to escape recognition by the host's immune response. Through the recombination of H. pylori's outer membrane proteins, immunoglobulins can no longer recognize these new structures and, therefore, cannot attack the antigen as part of the normal immune response. [2]

African trypanosomes

African trypanosomes are parasites that are able to escape the immune responses of its host animal through a range of mechanisms. Its most prevalent mechanism is its ability to evade recognition by antibodies through antigenic variation. This is achieved through the switching of its variant surface glycoprotein or VSG, a substance that coats the entire antigen. When this coat is recognized by an antibody, the parasite can be eliminated. However, variation of this coat can lead to antibodies being unable to recognize and eliminate the antigen. In addition to this, the VSG coat is able to clear the antibodies themselves to escape their clearing function.[ citation needed ][ clarification needed ]

Trypanosomes are also able to achieve evasion through the mediation of the host's immune response. Through the conversion of ATP to cAMP by the enzyme adenylate cyclase, the production of TNF-α, a signaling cytokine important for inducing inflammation, is inhibited in liver myeloid cells. In addition, trypanosomes are able to weaken the immune system by inducing B cell apoptosis (cell death) and the degradation of B cell lymphopoiesis. They are also able to induce suppressor molecules that can inhibit T cell reproduction. [3]

Plant RNA viruses

Lafforgue et al 2011 found escape mutants in plant RNA viruses to be encouraged by coexistence of transgenic crops with artificial microRNA (amiR)-based resistance with fully susceptible individuals of the same crop, and even more so by coexistence with weakly amiR-producing transgenics. [7] [8] [9] [10]

Tumor escape

Many head and neck cancers are able to escape immune responses in a variety of ways. One such example is through the production of pro-inflammatory and immunosuppressive cytokines. This can be achieved when the tumor recruits immunosuppressive cell subsets into the tumor's environment. Such cells include pro-tumor M2 macrophages, myeloid-derived suppressor cells (MDSCs), Th-2 polarized CD4 T-lymphocytes, and regulatory T-lymphocytes. These cells can then limit the responses of T cells through the production of cytokines and by releasing immune-modulating enzymes. [1] Additionally tumors can escape antigen-directed therapies by loss or down-regulation of the associated antigens, as well demonstrated after checkpoint blockade immunotherapy [11] and CAR-T cell therapy [12] though more recent data indicate that this may be prevented by localized bystander killing mediated by fasL/fas. [13] Alternatively therapies can be developed to encompass multiple antigens in parallel. [14]

Escape from vaccination

Consequences of recent vaccines

While vaccines are created to strengthen the immune response to pathogens, in many cases these vaccines are not able to cover the wide variety of strains a pathogen may have. Instead they may only protect against one or two strains, leading to the escape of strains not covered by the vaccine. [5] This results in the pathogens being able to attack targets of the immune system different than those intended to be targeted by the vaccination. [4] This parasitic antigen diversity is particularly troublesome for the development of the malaria vaccines. [5]

Solutions to escape of vaccination

In order to fix this problem, vaccines must be able to cover the wide variety of strains within a bacterial population. In recent research of Neisseria meningitidis , the possibility of such broad coverage may be achieved through the combination of multi-component polysaccharide conjugate vaccines. However, in order to further improve upon broadening the scope of vaccinations, epidemiological surveillance must be conducted to better detect the variation of escape mutants and their spread. [4]

See also

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

<span class="mw-page-title-main">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific 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 is one of the two main immunity strategies found in vertebrates.

<span class="mw-page-title-main">Original antigenic sin</span> Immune phenomenon

Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, immunological imprinting, or primary addiction is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin.

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

<i>Murine respirovirus</i> Sendai virus, virus of rodents

Murine respirovirus, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen 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 response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

Active immunotherapy is a type of immunotherapy that aims to stimulate the host's immune system or a specific immune response to a disease or pathogen and is most commonly used in cancer treatments. Active immunotherapy is also used for treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Active immunotherapies induce an immune response through direct immune system stimulation, while immunotherapies that administer antibodies directly to the system are classified as passive immunotherapies. Active immunotherapies can elicit generic and specific immune responses depending on the goal of the treatment. The categories of active immunotherapy divide into:

<span class="mw-page-title-main">Variant surface glycoprotein</span>

Variant surface glycoprotein (VSG) is a ~60kDa protein which densely packs the cell surface of protozoan parasites belonging to the genus Trypanosoma. This genus is notable for their cell surface proteins. They were first isolated from Trypanosoma brucei in 1975 by George Cross. VSG allows the trypanosomatid parasites to evade the mammalian host's immune system by extensive antigenic variation. They form a 12–15 nm surface coat. VSG dimers make up ~90% of all cell surface protein and ~10% of total cell protein. For this reason, these proteins are highly immunogenic and an immune response raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant. However, with each cell division there is a possibility that the progeny will switch expression to change the VSG that is being expressed. VSG has no prescribed biochemical activity.

Immunodominance is the immunological phenomenon in which immune responses are mounted against only a few of the antigenic peptides out of the many produced. That is, despite multiple allelic variations of MHC molecules and multiple peptides presented on antigen presenting cells, the immune response is skewed to only specific combinations of the two. Immunodominance is evident for both antibody-mediated immunity and cell-mediated immunity. Epitopes that are not targeted or targeted to a lower degree during an immune response are known as subdominant epitopes. The impact of immunodominance is immunodomination, where immunodominant epitopes will curtail immune responses against non-dominant epitopes. Antigen-presenting cells such as dendritic cells, can have up to six different types of MHC molecules for antigen presentation. There is a potential for generation of hundreds to thousands of different peptides from the proteins of pathogens. Yet, the effector cell population that is reactive against the pathogen is dominated by cells that recognize only a certain class of MHC bound to only certain pathogen-derived peptides presented by that MHC class. Antigens from a particular pathogen can be of variable immunogenicity, with the antigen that stimulates the strongest response being the immunodominant one. The different levels of immunogenicity amongst antigens forms what is known as dominance hierarchy.

<span class="mw-page-title-main">Nina Papavasiliou</span> Immunologist

Nina Papavasiliou is an immunologist and Helmholtz Professor in the Division of Immune Diversity at the German Cancer Research Center in Heidelberg, Germany. She is also an adjunct professor at the Rockefeller University, where she was previously associate professor and head of the Laboratory of Lymphocyte Biology. She is best known for her work in the fields of DNA and RNA editing.

mRNA vaccine Type of vaccine

An mRNAvaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen or by a cancer cell. These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.

A genetic vaccine is a vaccine that contains nucleic acids such as DNA or RNA that lead to protein biosynthesis of antigens within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and viral vector vaccines.

References

  1. 1 2 Allen, Clint; Clavijo, Paul; Waes, Carter; Chen, Zhong (2015). "Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches". Cancers. 7 (4): 2397–414. doi: 10.3390/cancers7040900 . PMC   4695900 . PMID   26690220.
  2. 1 2 Hanada, Katsuhiro; Yamaoda, Yoshio (2014). "Genetic Battle between Helicobacter pylori and humans. The Mechanism Underlying Homologous Recombination in Bacteria, Which Can Infect Human Cells". Microbes and Infection. 16 (10): 833–839. doi:10.1016/j.micinf.2014.08.001. PMID   25130723.
  3. 1 2 Cnops, Jennifer; Magez, Stefan; De Trez, Carl (2015). "Escape Mechanisms of African Trypanosomes: Why Trypanosomosis Is Keeping Us Awake". Parasitology. 142 (3): 417–427. doi:10.1017/s0031182014001838. PMID   25479093. S2CID   9365261.
  4. 1 2 3 4 Barnett, Timothy; Lim, Jin; Soderholm, Amelia; Rivera-Hernandes, Tania; West, Nicholas; Walker, Mark (2015). "Host-Pathogen Interaction During Bacterial Vaccination". Current Opinion in Immunology. 36: 1–7. doi:10.1016/j.coi.2015.04.002. PMID   25966310.
  5. 1 2 3 4 Barry, Alyssa; Arnott, Alicia (2014). "Strategies for Designing and Monitoring Malaria Vaccines Targeting Diverse Antigens". Frontiers in Immunology. 5: 359. doi: 10.3389/fimmu.2014.00359 . PMC   4112938 . PMID   25120545.
  6. ↑ Zimmer, Carl (12 May 2021). "Scientists warn U.S. lawmakers about the continued threat of coronavirus variants". The New York Times . Retrieved 13 May 2021.
  7. ↑ Lafforgue, Guillaume; et al. (9 September 2011). "Tempo and Mode of Plant RNA Virus Escape from RNA Interference-Mediated Resistance". Journal of Virology. 85 (19): 9686–9695. doi:10.1128/JVI.05326-11. PMC   3196453 . PMID   21775453.
  8. ↑ Bedhomme, Stéphanie; Hillung, Julia; Elena, Santiago F (2015). "Emerging viruses: why they are not jacks of all trades?". Current Opinion in Virology . Elsevier. 10: 1–6. doi:10.1016/j.coviro.2014.10.006. hdl: 10261/108773 . ISSN   1879-6257. PMID   25467278. S2CID   28445949.
  9. ↑ Duffy, Siobain (2018-08-13). "Why are RNA virus mutation rates so damn high?". PLOS Biology . Public Library of Science. 16 (8): e3000003. doi: 10.1371/journal.pbio.3000003 . ISSN   1545-7885. PMC   6107253 . PMID   30102691. S2CID   51978497.
  10. ↑ Elena, Santiago F.; Fraile, Aurora; García-Arenal, Fernando (2014). "3 - Evolution and Emergence of Plant Viruses". Advances in Virus Research . Vol. 88. Elsevier. pp. 161–191. doi:10.1016/B978-0-12-800098-4.00003-9. hdl:10251/58029. ISBN   978-0-12-800098-4. ISSN   0065-3527. PMID   24373312. S2CID   43840370.
  11. ↑ Zaretsky, Jesse M.; Garcia-Diaz, Angel; Shin, Daniel S.; Escuin-Ordinas, Helena; Hugo, Willy; Hu-Lieskovan, Siwen; Torrejon, Davis Y.; Abril-Rodriguez, Gabriel; Sandoval, Salemiz; Barthly, Lucas; Saco, Justin (2016-09-01). "Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma". The New England Journal of Medicine. 375 (9): 819–829. doi:10.1056/NEJMoa1604958. ISSN   1533-4406. PMC   5007206 . PMID   27433843.
  12. ↑ Majzner, Robbie G.; Mackall, Crystal L. (2018-10-01). "Tumor Antigen Escape from CAR T-cell Therapy". Cancer Discovery. 8 (10): 1219–1226. doi: 10.1158/2159-8290.CD-18-0442 . ISSN   2159-8274. PMID   30135176.
  13. ↑ Upadhyay, Ranjan; Boiarsky, Jonathan A.; Pantsulaia, Gvantsa; Svensson-Arvelund, Judit; Lin, Matthew J.; Wroblewska, Aleksandra; Bhalla, Sherry; Scholler, Nathalie; Bot, Adrian; Rossi, John M.; Sadek, Norah (2020-01-01). "A critical role for fas-mediated off-target tumor killing in T cell immunotherapy". Cancer Discovery. 11 (3): 599–613. doi: 10.1158/2159-8290.CD-20-0756 . ISSN   2159-8274. PMC   7933082 . PMID   33334730.
  14. ↑ Shah, Nirav N.; Johnson, Bryon D.; Schneider, Dina; Zhu, Fenlu; Szabo, Aniko; Keever-Taylor, Carolyn A.; Krueger, Winfried; Worden, Andrew A.; Kadan, Michael J.; Yim, Sharon; Cunningham, Ashley (October 2020). "Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial". Nature Medicine. 26 (10): 1569–1575. doi:10.1038/s41591-020-1081-3. ISSN   1546-170X. PMID   33020647. S2CID   222159001.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.