title: Bean (film)

text: Bean (also known as Bean: The Ultimate Disaster Movie or Bean: The Movie) is a 1997 comedy film directed by Mel Smith and written by Richard Curtis and Robin Driscoll. Based on the British sitcom series "Mr. Bean" created by Rowan Atkinson and Curtis, the film stars Atkinson in the title role, with Peter MacNicol, Pamela Reed, Harris Yulin, Sandra Oh and Burt Reynolds in supporting roles. In the film, Bean works as a security guard at the National Gallery in London before being sent to the United States to talk about the unveiling of James Abbott McNeill Whistler's 1871 painting "Whistler's Mother".


title: Bean (film)

text: Produced by Gramercy Pictures, Working Title Films, and Tiger Aspect Films, "Bean" was released in the United Kingdom on 2 August 1997 and in the United States on 7 November 1997 by PolyGram Filmed Entertainment and Universal Pictures. The film received mixed reviews from critics but was a box-office success, having grossed $251.2 million worldwide against an $18 million budget. A standalone sequel, "Mr. Bean's Holiday", was released in 2007.


title: Bean (film)

text: Well-meaning yet clumsy and destructive Mr. Bean works as a security guard at the National Gallery in London. When the gallery's board of directors, who despise Bean for sleeping on the job, fail to fire him under the chairman's orders, they instead select Bean as their representative for the transfer of James McNeill Whistler's 1871 portrait "Arrangement in Grey and Black No.1" ("Whistler's Mother") to the Grierson Art Gallery in Los Angeles, purchased by philanthropist General Newton for $50 million, in an attempt to get rid of him for a while.


title: Bean (film)

text: Grierson's curator David Langley, impressed with the false profile of "Dr. Bean", offers to accommodate Bean in his home for two months against his family's wishes. After Bean pranks the airport police by pretending to have a gun and accidentally destroys the family's prized possessions, David's wife, Alison, leaves for her mother's house along with their children, Kevin and Jennifer. David then begins to question Bean's status as an art expert following a visit to Pacific Park, where Bean is arrested by Lieutenant Brutus - the same police officer who interrogated him at the airport - after speeding up a simulator ride to make it more exciting for him. After Bean accidentally ruins a dinner with Mr. Grierson and his wife, David discovers that Bean is not a doctor and knows nothing about art.


title: Bean (film)

text: The next day, Bean accidentally sneezes on "Whistler's Mother" and damages the painting with an ink-stained tissue and lacquer thinner while cleaning it. Fearing that the damage would cost him his job and possibly get him prosecuted, David becomes despondent and gets drunk with Bean, though his family returns out of pity. That night, determined to save David's career, Bean sneaks back into the gallery, incapacitates the security guard with laxatives and replaces the defaced "Whistler's Mother" with a reprinted poster of it coated in egg whites and nail polish to resemble the real one, which successfully fools everyone at the ceremony the next day. Bean gives a speech about the painting, expressing an improvised and sentimental opinion about it that wins the crowd's approval.


title: Bean (film)

text: Brutus informs David that Jennifer has recently got into a motorcycle accident with her boyfriend, prompting David and Bean to rush to the hospital. While wandering around the hospital, Bean gets mistaken for a surgeon and is forced into a surgery room, where he encounters Brutus - who has been shot while dealing with a mugging on the way to the hospital - and saves his life by inadvertently removing the bullet from his body. David then begs Bean, unaware of his true identity, to wake Jennifer up from her unconscious state, in which he succeeds after an accident with a defibrillator sends Bean flying and landing on her. Grateful for having their daughter back and wondering how to repay their doctor, David and Alison are surprised when Bean reveals his true identity. Per Bean's suggestion, they repay him by allowing him to stay with them for one more week.


title: Bean (film)

text: Bean spends quality time together with David and his family, before David accompanies him back to the airport for his flight home to London and thanks him for everything as he departs. At home, Bean goes to sleep with his bedroom now decorated with photographs of his time in Los Angeles, as well as the original "Whistler's Mother" painting he smuggled back with him.


title: Bean (film)

text: In November 1991, a year after the original series premiered, "Variety" announced that 20th Century Fox was producing a film adaptation of "Mr. Bean" in association with the show's production company, Tiger Television, after the studio remade two sketches from the series into short films released theatrically, "Mr. Bean Takes an Exam" and "Mr. Bean Goes to a Première". The film was later instead produced by the UK-based Working Title Films and PolyGram Filmed Entertainment, under the latter's Gramercy Pictures banner.


title: Bean (film)

text: The North American release differs from the international release, as it includes an additional scene in which David suggests that Bean stuff the turkey while he distracts the Griersons during the dinner party. After losing his watch in the turkey, Bean gets his head stuck inside of it (a recycled gag from "Merry Christmas Mr. Bean") and stumbles blindly around the kitchen and the dining room.


title: Bean (film)

text: The international release includes two alternate scenes on either side of the deleted turkey scene in order to explain its absence. When searching the refrigerator, Bean first finds two frankfurters and then the onion that he offers as an appetizer. Upon finding the turkey, David asks him if he has cooked a turkey before and he replies, "Oh yes." After the two shove the turkey into the microwave oven, Bean suggests running it for 20 minutes as opposed to the 5-hour cooking time suggested by David, which cause the turkey to explode.


title: Bean (film)

text: According to Atkinson in the documentary "Bean Scenes Unseen", the differing scenes were the result of very different reactions from the North American and international audiences in test screenings.


title: Bean (film)

text: The film score was composed and conducted by Howard Goodall, who also composed the original "Mr. Bean" series, although the original Mr. Bean theme was unused. Cover versions on the soundtrack album include the Beatles' "Yesterday" (sung by Wet Wet Wet), the OMC cover of "I Love L.A." (though Randy Newman's original version is the one heard in the film), and Alice Cooper's "Elected", performed by Iron Maiden lead singer Bruce Dickinson. "Elected" features sound dubs of Mr. Bean making campaign promises and was previously used in Comic Relief in 1992.


title: Bean (film)

text: "Bean" opened in Australia on 3 July 1997 and grossed $3.1 million in its opening weekend from 193 screens with a $16,062 per-theater average, placing number one for the weekend. It remained number one for a second week. In the UK, it opened on 8 August 1997 on 345 screens and grossed £2,563,326 ($4.0 million) (including previews of £284,936) with a £7,430 ($11,719) per-theater average, finishing second for the weekend behind the second weekend of "Men in Black". It was the highest opening gross for a British production surpassing the £1.4 million opening of "Four Weddings and a Funeral". In Germany, it grossed 12.3 million Deutsche mark ($6.8 million) from 682 screens with a $9,998 per-theater average to take the number one spot, beating fellow opener "The Fifth Element". It remained number one for a second week in Germany. It became the fastest UK film to gross $100 million and reached that milestone before opening in the US.


title: Bean (film)

text: It opened in Canada on 17 October 1997 in 242 theaters and grossed $2,255,233 with a $9,319 per-theater average and ranking number 10 at the US and Canadian box office, the first Canadian only release to reach the US and Canadian top 10. On its release in the United States on 7 November 1997, the film grossed $12,733,827 in its opening weekend while playing in 1,948 theaters, with a $6,536 per-theater average and ranking second behind "Starship Troopers". Due to the R rating of "Starship Troopers", its underperformance and "Bean" exceeding expectations, there were claims that under 17s may have bought tickets for "Bean" and snuck in to see "Starship Troopers".


title: Bean (film)

text: By the end its theatrical run, the film had grossed £17,902,161 in the UK, the fourth highest-grossing film for the year. It grossed $45,319,423 in the United States and Canada and $251,212,670 worldwide.


title: Bean (film)

text: On Rotten Tomatoes, the film holds an approval rating of 44% based on 34 reviews with an average rating of 5.32/10. The site's critical consensus reads: ""Bean" boasts a terrifically talented physical comedian in the title role, but his constant mugging and silly slapstick quickly wear thin." On Metacritic the film holds a score of 52 out of 100 based on 20 critics, indicating "mixed or average reviews".


title: Bean (film)

text: Roger Ebert gave the film two-and-a-half stars out of four, saying that while he praised the film for having "many moments that were very funny", he criticized the film's runtime of 90 minutes, saying it was too long: "At an hour, "Bean" would have been nonstop laughs. [But] then they added 30 minutes of stops."


title: Bean (film)

text: A standalone sequel, titled "Mr. Bean's Holiday", was released in 2007, ten years after its predecessor's release.


title: Squamata

text: Squamata (, Latin "squamatus", 'scaly, having scales') is the largest order of reptiles, comprising lizards, snakes, and amphisbaenians (worm lizards), which are collectively known as squamates or scaled reptiles. With over 10,900 species, it is also the second-largest order of extant (living) vertebrates, after the perciform fish. Members of the order are distinguished by their skins, which bear horny scales or shields, and must periodically engage in molting. They also possess movable quadrate bones, making possible movement of the upper jaw relative to the neurocranium. This is particularly visible in snakes, which are able to open their mouths very wide to accommodate comparatively large prey. Squamata is the most variably sized order of reptiles, ranging from the dwarf gecko ("Sphaerodactylus ariasae") to the Reticulated python ("Malayopython reticulatus") and the now-extinct mosasaurs, which reached lengths over .


title: Squamata

text: Among other reptiles, squamates are most closely related to the tuatara, the last surviving member of the once diverse Rhynchocephalia, with both groups being placed in the clade Lepidosauria.


title: Squamata

text: Squamates are a monophyletic sister group to the rhynchocephalians, members of the order Rhynchocephalia. The only surviving member of the Rhynchocephalia is the tuatara. Squamata and Rhynchocephalia form the subclass Lepidosauria, which is the sister group to the Archosauria, the clade that contains crocodiles and birds, and their extinct relatives. Fossils of rhynchocephalians first appear in the Early Triassic, meaning that the lineage leading to squamates must have also existed at the time. Scientists believe crown group squamates probably originated in the Early Jurassic based on the fossil record, The first fossils of geckos, skinks, and snakes appear in the Middle Jurassic. and their overall diversity was established during the mid-Jurassic, with further diversity expansions being mostly the result of added species. Other groups like iguanians and varanoids appeared in the Cretaceous. Polyglyphanodontia, an extinct clade of lizards, and mosasaurs, a group of predatory marine lizards that grew to enormous sizes, also appeared in the Cretaceous. Squamates suffered a mass extinction at the Cretaceous–Paleogene (K–PG) boundary, which wiped out polyglyphanodontians, mosasaurs, and many other distinct lineages.


title: Squamata

text: The relationships of squamates is debatable. Although many of the groups originally recognized on the basis of morphology are still accepted, understanding of their relationships to each other has changed radically as a result of studying their genomes. Iguanians were long thought to be the earliest crown group squamates based on morphological data, but genetic data suggest that geckoes are the earliest crown group squamates. Iguanians are now united with snakes and anguimorphs in a clade called Toxicofera. Genetic data also suggest that the various limbless groups - snakes, amphisbaenians, and dibamids - are unrelated, and instead arose independently from lizards.


title: Squamata

text: A study in 2018 found that "Megachirella", an extinct genus of lepidosaurs that lived about 240 million years ago during the Middle Triassic, was a stem-squamate, making it the oldest known squamate. The phylogenetic analysis was conducted by performing high-resolution microfocus X-ray computed tomography (micro-CT) scans on the fossil specimen of "Megachirella" to gather detailed data about its anatomy. These data were then compared with a phylogenetic dataset combining the morphological and molecular data of 129 extant and extinct reptilian taxa. The comparison revealed "Megachirella" had certain features that are unique to squamates. The study also found that geckos are the earliest crown group squamates, not iguanians.


title: Squamata

text: In 2022, the extinct genus "Cryptovaranoides" was described from the Late Triassic of England. "Cryptovaranoides" appears to be a highly derived squamate belonging to the group Anguimorpha, which contains many extant lineages such as monitor lizards, beaded lizards and anguids. The presence of an essentially modern crown group squamate so far back in time indicates that the diversification of squamate lineages, which was previously thought to have occurred during the Jurassic and Cretaceous, occurred much earlier than previously theorized. The Triassic squamate diversification is thought to be linked to the Carnian Pluvial Episode, which was responsible for the diversification of many other groups of insects, plants, and vertebrates.


title: Squamata

text: The male members of the group Squamata have hemipenes, which are usually held inverted within their bodies, and are everted for reproduction via erectile tissue like that in the mammalian penis. Only one is used at a time, and some evidence indicates that males alternate use between copulations. The hemipenis has a variety of shapes, depending on the species. Often it bears spines or hooks, to anchor the male within the female. Some species even have forked hemipenes (each hemipenis has two tips). Due to being everted and inverted, hemipenes do not have a completely enclosed channel for the conduction of sperm, but rather a seminal groove that seals as the erectile tissue expands. This is also the only reptile group in which both viviparous and ovoviviparous species are found, as well as the usual oviparous reptiles. Some species, such as the Komodo dragon, can reproduce asexually through parthenogenesis.


title: Squamata

text: Studies have been conducted on how sexual selection manifests itself in snakes and lizards. Snakes use a variety of tactics in acquiring mates. Ritual combat between males for the females with which they want to mate includes topping, a behavior exhibited by most viperids, in which one male twists around the vertically elevated fore body of his opponent and forcing it downward. Neck biting commonly occurs while the snakes are entwined.


title: Squamata

text: Parthenogenesis is a natural form of reproduction in which the growth and development of embryos occur without fertilization. "Agkistrodon contortrix" (copperhead snake) and "Agkistrodon piscivorus" (cottonmouth snake) can reproduce by facultative parthenogenesis; they are capable of switching from a sexual mode of reproduction to an asexual mode. The type of parthenogenesis that likely occurs is automixis with terminal fusion (see figure), a process in which two terminal products from the same meiosis fuse to form a diploid zygote. This process leads to genome-wide homozygosity, expression of deleterious recessive alleles, and often to developmental abnormalities. Both captive-born and wild-born "A. contortrix" and "A. piscivorus" appear to be capable of this form of parthenogenesis.


title: Squamata

text: Reproduction in squamate reptiles is ordinarily sexual, with males having a ZZ pair of sex-determining chromosomes, and females a ZW pair. However, the Colombian rainbow boa, "Epicrates maurus", can also reproduce by facultative parthenogenesis, resulting in production of WW female progeny. The WW females are likely produced by terminal automixis.


title: Squamata

text: When female sand lizards mate with two or more males, sperm competition within the female's reproductive tract may occur. Active selection of sperm by females appears to occur in a manner that enhances female fitness. On the basis of this selective process, the sperm of males that are more distantly related to the female are preferentially used for fertilization, rather than the sperm of close relatives. This preference may enhance the fitness of progeny by reducing inbreeding depression.


title: Squamata

text: Recent research suggests that the evolutionary origin of venom may exist deep in the squamate phylogeny, with 60% of squamates placed in this hypothetical group called Toxicofera. Venom has been known in the clades Caenophidia, Anguimorpha, and Iguania, and has been shown to have evolved a single time along these lineages before the three groups diverged, because all lineages share nine common toxins. The fossil record shows the divergence between anguimorphs, iguanians, and advanced snakes dates back roughly 200 million years ago (Mya) to the Late Triassic/Early Jurassic, but the only good fossil evidence is from the Middle Jurassic.


title: Squamata

text: Snake venom has been shown to have evolved via a process by which a gene encoding for a normal body protein, typically one involved in key regulatory processes or bioactivity, is duplicated, and the copy is selectively expressed in the venom gland. Previous literature hypothesized that venoms were modifications of salivary or pancreatic proteins, but different toxins have been found to have been recruited from numerous different protein bodies and are as diverse as their functions.


title: Squamata

text: Natural selection has driven the origination and diversification of the toxins to counter the defenses of their prey. Once toxins have been recruited into the venom proteome, they form large, multigene families and evolve via the birth-and-death model of protein evolution, which leads to a diversification of toxins that allows the ambush predators the ability to attack a wide range of prey. The rapid evolution and diversification is thought to be the result of a predator–prey evolutionary arms race, where both are adapting to counter the other.


title: Squamata

text: An estimated 125,000 people a year die from venomous snake bites. In the US alone, more than 8,000 venomous snake bites are reported each year, but only one in 50 million people (five or six fatalities per year in the USA) will die from venomous snake bites.


title: Squamata

text: Lizard bites, unlike venomous snake bites, are usually not fatal. The Komodo dragon has been known to kill people due to its size, and recent studies show it may have a passive envenomation system. Recent studies also show that the close relatives of the Komodo, the monitor lizards, all have a similar envenomation system, but the toxicity of the bites is relatively low to humans. The Gila monster and beaded lizards of North and Central America are venomous, but not deadly to humans.


title: Squamata

text: Though they survived the Cretaceous–Paleogene extinction event, many squamate species are now endangered due to habitat loss, hunting and poaching, illegal wildlife trading, alien species being introduced to their habitats (which puts native creatures at risk through competition, disease, and predation), and other anthropogenic causes. Because of this, some squamate species have recently become extinct, with Africa having the most extinct species. Breeding programs and wildlife parks, though, are trying to save many endangered reptiles from extinction. Zoos, private hobbyists, and breeders help educate people about the importance of snakes and lizards.


title: Squamata

text: Of these, the lizards form a paraphyletic group, since "lizards" excludes the subclades of snakes and amphisbaenians. Studies of squamate relationships using molecular biology have found several distinct lineages, though the specific details of their interrelationships vary from one study to the next. One example of a modern classification of the squamates is


title: Squamata

text: All recent molecular studies suggest that several groups form a venom clade, which encompasses a majority (nearly 60%) of squamate species. Named Toxicofera, it combines the groups Serpentes (snakes), Iguania (agamids, chameleons, iguanids, etc.), and Anguimorpha (monitor lizards, Gila monster, glass lizards, etc.).


title: Camelot

text: Camelot is a castle and court associated with the legendary King Arthur. Absent in the early Arthurian material, Camelot first appeared in 12th-century French romances and, since the Lancelot-Grail cycle, eventually came to be described as the fantastic capital of Arthur's realm and a symbol of the Arthurian world.


title: Camelot

text: The stories locate it somewhere in Great Britain and sometimes associate it with real cities, though more usually its precise location is not revealed. Most scholars regard it as being entirely fictional, its unspecified geography being perfect for chivalric romance writers. Nevertheless, arguments about the location of the "real Camelot" have occurred since the 15th century and continue today in popular works and for tourism purposes.


title: Camelot

text: The name's derivation is uncertain. It has numerous different spellings in medieval French Arthurian romances, including "Camaalot", "Camalot", "Chamalot", "Camehelot" (sometimes read as "Camchilot"), "Camaaloth", "Caamalot", "Camahaloth", "Camaelot", "Kamaalot", "Kamaaloth", "Kaamalot", "Kamahaloth", "Kameloth", "Kamaelot", "Kamelot", "Kaamelot", "Cameloth", and "Gamalaot". Arthurian scholar Ernst Brugger suggested that it was a corruption of the site of Arthur's final battle, the Battle of Camlann, in Welsh tradition. Roger Sherman Loomis believed it was derived from "Cavalon", a place name that he suggested was a corruption of Avalon (under the influence of the Breton place name "Cavallon"). He further suggested that Cavalon became Arthur's capital due to confusion with Arthur's other traditional court at Caerleon ("Caer Lleon" in Welsh).


title: Camelot

text: Others have suggested a derivation from the British Iron Age and Romano-British place name Camulodunum, one of the first capitals of Roman Britain and which would have significance in Romano-British culture. Indeed, John Morris, the English historian who specialized in the study of the institutions of the Roman Empire and the history of Sub-Roman Britain, suggested in his book "The Age of Arthur" that as the descendants of Romanized Britons looked back to a golden age of peace and prosperity under Rome, the name "Camelot" of Arthurian legend may have referred to the capital of Britannia (Camulodunum) in Roman times. It is unclear, however, where Chrétien de Troyes would have encountered the name Camulodunum, or why he would render it as "Camaalot", though Urban T. Holmes argued in 1929 that Chrétien had access to Book 2 of Pliny's "Natural History", where it is rendered as "Camaloduno". Given Chrétien's known tendency to create new stories and characters, being the first to mention the hero Lancelot's love affair with Queen Guinevere for example, the name might also be entirely invented.


title: Camelot

text: Arthur's court at Camelot is mentioned for the first time in Chrétien's poem "Lancelot, the Knight of the Cart", dating to the 1170s, though it does not appear in all the manuscripts. In the C manuscript (Paris, Bibliothèque Nationale de France, fonds français 794, folio 27r), which might in fact contain the proper reading of Chretien's original text, instead of the place name we find the Old French phrase "con lui plot", meaning "as he pleased". The other manuscripts spell the name variously as "Chamalot" (MS A, f. f. 196r), "Camehelot" (MS E, f. 1r), "Chamaalot" (MS G, f. 34f), and "Camalot" (MS T, f. 41v); the name is missing, along with the rest of the passage containing it, in MS V (Vatican, Biblioteca Vaticana, Regina 1725). Camelot is mentioned only in passing and is not described:


title: Camelot

text: Nothing in Chrétien's poem suggests the level of importance Camelot would have in later romances. For Chrétien, Arthur's chief court was in Caerleon in Wales; this was the king's primary base in Geoffrey of Monmouth's "Historia Regum Britanniae" and subsequent literature. Chrétien depicts Arthur, like a typical medieval monarch, holding court at a number of cities and castles.


title: Camelot

text: It is not until the 13th-century French prose romances, including the Vulgate and Post-Vulgate cycles, that Camelot began to supersede Caerleon, and even then, many descriptive details applied to Camelot derive from Geoffrey's earlier grand depiction of the Welsh town. Most Arthurian romances of this period produced in English or Welsh did not follow this trend; Camelot was referred to infrequently, and usually in translations from French. One exception is "Sir Gawain and the Green Knight", which locates Arthur's court at "Camelot"; however, in Britain, Arthur's court was generally located at Caerleon, or at Carlisle, which is usually identified with the "Carduel" of the French romances.


title: Camelot

text: The "Lancelot-Grail" cycle and the texts it influenced depict the city of Camelot as standing along a river, downstream from Astolat. It is surrounded by plains and forests, and its magnificent cathedral, St. Stephen's, originally established by Josephus, the son of Joseph of Arimathea, is the religious centre for Arthur's Knights of the Round Table. There, Arthur and Guinevere are married and there are the tombs of many kings and knights. In a mighty castle stands the Round Table, created by Merlin and Uther Pendragon; it is here that Galahad conquers the Siege Perilous, and where the knights see a vision of the Holy Grail and swear to find it. Jousts are often held in a meadow outside the city.


title: Camelot

text: Its imprecise geography serves the romances well, as Camelot becomes less a literal place than a powerful symbol of Arthur's court and universe. There is also a Kamaalot featured as the home of Percival's mother in the romance "Perlesvaus". In "Palamedes" and some other works, including the Post-Vulgate cycle, King Arthur's Camelot is eventually razed to the ground by the treacherous King Mark of Cornwall (who had besieged it earlier) in his invasion of Logres after the Battle of Camlann. In the "Tavola Ritonda", Camelot falls to ruin after the death of Arthur.


title: Camelot

text: From Geoffrey's grand description of Caerleon, Camelot gains its impressive architecture, its many churches and the chivalry and courtesy of its inhabitants. Geoffrey's description in turn drew on an already established tradition in Welsh oral tradition of the grandeur of Arthur's court. The tale "Culhwch and Olwen", associated with the "Mabinogion" and perhaps first written in the 11th century, draws a dramatic picture of Arthur's hall and his many powerful warriors who go from there on great adventures, placing it in Celliwig, an uncertain locale in Cornwall.


title: Camelot

text: Although the court at Celliwig is the most prominent in remaining early Welsh manuscripts, the various versions of the Welsh Triads agree in giving Arthur multiple courts, one in each of the areas inhabited by the Celtic Britons: Cornwall, Wales and the Hen Ogledd. This perhaps reflects the influence of widespread oral traditions common by the 9th century which are recorded in various place names and features such as Arthur's Seat, indicating Arthur was a hero known and associated with many locations across Brittonic areas of Britain as well as Brittany. Even at this stage Arthur could not be tied to one location. Many other places are listed as a location where Arthur holds court in the later romances, Carlisle and London perhaps being the most prominent.


title: Camelot

text: In the 15th century, the English writer Thomas Malory created the image of Camelot most familiar today in his "Le Morte d'Arthur", a work based mostly on the French romances. He firmly identifies Camelot with Winchester in England, an identification that remained popular over the centuries, though it was rejected by Malory's own editor, William Caxton, who preferred a Welsh location.


title: Camelot

text: Arthurian scholar Norris J. Lacy commented that "Camelot, located no where in particular, can be anywhere." The romancers' versions of Camelot draw on earlier traditions of Arthur's fabulous court. The Celliwig of "Culhwch and Olwen" appears in the Welsh Triads as well; this early Welsh material places Wales' greatest leader outside its national boundaries. Geoffrey's description of Caerleon is probably based on his personal familiarity with the town and its Roman ruins; it is less clear that Caerleon was associated with Arthur before Geoffrey. Several French romances ("Perlesvaus", the Didot "Perceval" attributed to Robert de Boron, and even the early romances of Chrétien such as "Erec and Enide" and "Yvain, the Knight of the Lion") have Arthur hold court at "Carduel in Wales", a northern city based on the real Carlisle. Malory's identification of Camelot as Winchester was probably partially inspired by the latter city's history: it had been the capital of Wessex under Alfred the Great, and boasted the Winchester Round Table, an artifact constructed in the 13th century but widely believed to be the original by Malory's time. Caxton rejected the association, saying Camelot was in Wales and that its ruins could still be seen; this is a likely reference to the Roman ruins at Caerwent.


title: Camelot

text: In 1542, John Leland reported that the locals around Cadbury Castle (formerly known as Camalet) in Somerset considered it to be the original Camelot. This theory, which was repeated by later antiquaries, is bolstered, or may have derived from, Cadbury's proximity to the River Cam and the villages of Queen Camel and West Camel, and remained popular enough to help inspire a large-scale archaeological dig in the 20th century. These excavations, led by archaeologist Leslie Alcock from 1966 to 1970, were titled "Cadbury-Camelot" and won much media attention. The dig revealed that the site seems to have been occupied as early as the 4th millennium BC and to have been refortified and occupied by a major Brittonic ruler and his war band from . This early medieval settlement continued until around 580. The works were by far the largest known fortification of the period, double the size of comparative "caers" and with Mediterranean artifacts representing extensive trade and Saxon ones showing possible conquest. The use of the name Camelot and the support of Geoffrey Ashe helped ensure much publicity for the finds, but Alcock himself later grew embarrassed by the supposed Arthurian connection to the site. Following the arguments of David Dumville, Alcock felt the site was too late and too uncertain to be a tenable Camelot. Modern archaeologists follow him in rejecting the name, calling it instead Cadbury Castle hill fort. Despite this, Cadbury remains widely associated with Camelot.


title: Camelot

text: The name of the Romano-British town of Camulodunum (modern Colchester) was derived from the Celtic god Camulus. However, it was located well within territory usually thought to have been conquered early in the 5th century by Saxons, so it is unlikely to have been the location of any "true" Camelot, as Arthur is traditionally dated to the late 5th and early 6th century. The town was definitely known as Colchester as early as the "Anglo-Saxon Chronicle" in 917. Even Colchester Museum argues strongly regarding the historical Arthur: "It would be impossible and inconceivable to link him to the Colchester area, or to Essex more generally," pointing out that the connection between the name Camulodunum and Colchester was unknown until the 18th century. Arthurian scholar Peter Field has suggested that another Camulodunum, a former Roman fort, is a likely location of King Arthur's Camelot and that "Slack, on the outskirts of Huddersfield in West Yorkshire," is where Arthur would have held court. This is because of the name, and also regarding its strategic location: it is but a few miles from the extreme south-west of Hen Ogledd (also making close to North Wales), and would have been a flagship point in staving off attacks to the Celtic kingdoms from the Angles and others.


title: Camelot

text: Other places in Britain with names related to "Camel" have also been suggested, such as Camelford in Cornwall, located down the River Camel from where Geoffrey places Camlann, the scene of Arthur's final battle. The area's connections with Camelot and Camlann are merely speculative. Further north, Camelon and its connections with Arthur's O'on have been mentioned in relation to Camelot, but Camelon may be an antiquarian neologism coined after the 15th century, with its earlier name being "Carmore" or "Carmure". Graham Phillips rejected the word "Camelot" entirely as just Chrétien's invention and instead proposed the old Roman city of Viroconium (near Shrewsbury in modern England) as Arthur's capital, citing archeological evidence of a grand palace having been in use around 500 AD. Alistair Moffat identified Camelot with Roxburgh in Scotland.


title: Camelot

text: Camelot has become a permanent fixture in modern interpretations of the Arthurian legend. The symbolism of Camelot so impressed Alfred, Lord Tennyson that he wrote up a prose sketch on the castle as one of his earliest attempts to treat the legend. Modern stories typically retain Camelot's lack of precise location and its status as a symbol of the Arthurian world, though they typically transform the castle itself into romantically lavish visions of a High Middle Ages palace. Some writers of the "realist" strain of modern Arthurian fiction have attempted a more sensible Camelot. Inspired by Alcock's Cadbury-Camelot excavation, some authors such as Marion Zimmer Bradley and Mary Stewart place their Camelots in that place and describe it accordingly.


title: Camelot

text: Camelot lends its name to the musical "Camelot", which was adapted into a film of the same title, featuring the Castle of Coca, Segovia as Camelot. An Arthurian television series "Camelot" was also named after the castle, as were some other works including the video game "Camelot" and the comic book series "Camelot 3000". French television series "Kaamelott" presents a humorous alternative version of the Arthurian legend; Camelot Theme Park is a now-abandoned Arthurian theme park resort located in the English county of Lancashire.


title: Camelot

text: In American contexts, Camelot refers to the presidency of John F. Kennedy. In a 1963 "Life" interview, Jacqueline, his widow, referenced a line from the Lerner and Loewe musical to describe the Kennedy era White House: "Don't let it be forgot, that once there was a spot, for one brief shining moment, that was known as Camelot." She indicated that it was one of Kennedy's favorite lyrics from the musical and added, "there'll be great Presidents again […] but there'll never be another Camelot again."


title: Rodrigo Bentancur

text: Rodrigo Bentancur Colman (born 25 June 1997) is an Uruguayan professional footballer who plays as a midfielder for club Tottenham Hotspur and the Uruguay national team.


title: Rodrigo Bentancur

text: He started his career in the youth system of Argentine side Boca Juniors in 2009. He was promoted to the senior squad in 2015, and won two Primera División titles and a Copa Argentina with the team. He was signed by Italian club Juventus in 2017, where he won three consecutive Serie A titles, among other trophies. In January 2022, Bentancur joined Tottenham Hotspur in the Premier League.


title: Rodrigo Bentancur

text: At international level, Bentancur was a member of the Uruguay U20 squad that won the 2017 South American U-20 Championship. He made his senior debut for Uruguay in 2017, representing the side at the FIFA World Cup in 2018 and 2022 and the Copa América in 2019 and 2021.


title: Rodrigo Bentancur

text: Bentancur is a product of the Boca Juniors youth academy. On 12 April 2015, he made his first team debut for the club in a league game against Nueva Chicago. He replaced Pablo Pérez after 77 minutes in a 0–0 home draw.


title: Rodrigo Bentancur

text: On 13 July 2015, Bentancur, Guido Vadalá, Franco Cristaldo and Adrián Cubas became part of Carlos Tevez's deal, which saw Juventus have the first option to sign the youngsters until 20 April 2017, with Vadalá also joining Juventus on loan for the 2015–2017 seasons. Bentancur was tagged for €9.4 million. Juventus's CEO Giuseppe Marotta later confirmed that Juventus would be exercising their option to sign Bentancur in 2017. He arrived in Turin on 3 April 2017 and completed his medical on the same day. On 21 April 2017 Juventus completed their acquisition of Bentancur, signing him on a five-year deal effective from 1 July 2017 until 30 June 2022 for a €9.5 million transfer fee, plus additional performance based bonuses. Boca Juniors are also entitled to 50% of any future transfer fee that Juventus receive for Bentancur. Bentancur subsequently returned to Argentina to play out the remainder of the 2016–17 season with Boca Juniors.


title: Rodrigo Bentancur

text: Bentancur formally became a player of Juventus on 1 July 2017, after the club activated the option to sign him in April 2017, in a deal which would keep him at the club until 2022. The first option to sign Bentancur was bought as part of Carlos Tevez's deal in July 2015. He made his club debut on 26 August 2017, coming on as a substitute in a 4–2 away win over Genoa in Serie A.


title: Rodrigo Bentancur

text: On 6 October 2018, Bentancur scored his first goal for the club in a 2–0 away win over Udinese in Serie A.


title: Rodrigo Bentancur

text: On 31 January 2022, Bentancur joined Premier League club Tottenham Hotspur for an undisclosed fee. Bentancur made his debut for Spurs on 5 February in the FA Cup match against Brighton & Hove Albion, coming on a substitute in match that finished in a 3–1 win. He made his Premier League debut nine days later, coming on as a substitute for Pierre-Emile Højbjerg in a 2–3 loss against Southampton. On 18 September 2022, Bentancur scored his first goal for the club in a Premier League game against Leicester City, the third goal in a 6–2 victory at the Tottenham Hotspur Stadium. Later on in the season, Bentancur scored his first UEFA Champions League goal in a group stage match - an equaliser against Sporting CP. The match ended 1–1. He continued his goal-scoring form in Spurs' league fixture three days later, coming off the bench to score an injury-time winner hagainst AFC Bournemouth, completing a 3–2 comeback after they had gone 2–0 down. Two weeks later he registered his first brace in the Premier League, with two late goals against Leeds United to secure a 4–3 victory for Spurs.


title: Rodrigo Bentancur

text: Bentancur was a member of Uruguay national under-20 team, winning 2017 South American U-20 Championship. The squad also finished as the fourth in 2017 FIFA U-20 World Cup.


title: Rodrigo Bentancur

text: In September 2017, Bentancur received his first senior call-up to the Uruguayan national team by manager Óscar Tabárez for the team's upcoming 2018 World Cup qualifiers against Venezuela and Bolivia in October. He made his international debut on 5 October, coming on as a substitute in Uruguay's 0–0 away draw against Venezuela. He was named in the squad for the China Cup in March 2018.


title: Rodrigo Bentancur

text: In May 2018, Bentancur was named in Uruguay's provisional 26-man squad for the 2018 FIFA World Cup in Russia. He was later included in the team's final 23-man squad for the tournament. He appeared in Uruguay's opening match of the tournament on 15 June, a 1–0 victory over Egypt at the Yekaterinburg Arena. In the Round of 16 match against Portugal on 30 June, he set-up Edinson Cavani's second goal in an eventual 2–1 victory. Uruguay were eliminated from the tournament following a 2–0 defeat to eventual champions France in the quarter-finals on 6 July.


title: Rodrigo Bentancur

text: In March 2019, Tabárez included Bentancur in the final 23-man Uruguay squad for the 2019 Copa América in Brazil. In the quarter-finals against Peru on 29 June, a 0–0 draw after regulation time saw the match go to a penalty shoot-out; although Bentancur was able to score his kick, Uruguay lost the shoot-out 4–5 and were eliminated from the competition.


title: Rodrigo Bentancur

text: A dynamic, hard-working, skillful, elegant, and tactically versatile midfielder, who is comfortable using either foot, Bentancur has been described as a tall and "physically strong" player, who is capable of playing in any midfield position, including as a defensive midfielder, as a central midfielder, as a winger on either flank, in a box-to-box role, or even as a mezzala, or as an attacking midfielder behind the forwards, due to his ability to make attacking runs from behind.


title: Rodrigo Bentancur

text: He also possesses good close control, technique, and quick footwork, which enable him to get past opponents when in possession, while his vision, intelligence, personality, and incisive passing also allow him to set the tempo of his team's play in a more creative role as a "regista" deep in midfield, and create goalscoring opportunities for his teammates after winning back the ball. His height and strong frame also enable him to act as a "target man" in an advanced midfield role; he has even played as a second striker on occasion.


title: Rodrigo Bentancur

text: Although his acceleration is not particularly impressive, he is also a mobile player, who is capable of pressing opponents further up the pitch. Moreover, he has also drawn praise in the media for his composure and quick-thinking both with and without the ball. Due to his precociousness, talent, maturity, and wide range of skills, he is considered to be a highly promising young player in the media.


title: Sarcoma

text: A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates. Sarcomas are "primary" connective tissue tumors, meaning that they arise in connective tissues. This is in contrast to "secondary" (or "metastatic") connective tissue tumors, which occur when a cancer from elsewhere in the body (such as the lungs, breast tissue or prostate) spreads to the connective tissue. The word "sarcoma" is derived from the Greek σάρκωμα "sarkōma" "fleshy excrescence or substance", itself from σάρξ "sarx" meaning "flesh".


title: Sarcoma

text: Sarcomas are typically divided into two major groups: bone sarcomas and soft-tissue sarcomas, each of which has multiple subtypes. In the United States, the American Joint Committee on Cancer (AJCC) publishes guidelines that classify the subtypes of sarcoma. These subtypes are as follows:


title: Sarcoma

text: Symptoms of bone sarcomas typically include bone pain, especially at night, and swelling around the site of the tumor.


title: Sarcoma

text: Symptoms of soft-tissue sarcomas vary, but they often present as firm, painless lumps or nodules. Gastrointestinal stromal tumors (a subtype of soft tissue sarcoma) often are asymptomatic, but can be associated with vague complaints of abdominal pain, a feeling of fullness, or other signs of intestinal obstruction.


title: Sarcoma

text: The cause of most bone sarcomas is not known, but several factors are associated with an increased risk of developing bone sarcoma. Previous exposure to ionizing radiation (such as prior radiation therapy) is one such risk factor. Exposure to alkylating agents, such as those found in certain cancer chemotherapeutic medicines, also increases the risk of bone sarcoma. Certain inherited genetic syndromes, including Li-Fraumeni syndrome, heritable RB1 gene mutations, and Paget's disease of bone, are associated with an increased risk of developing bone sarcomas.


title: Sarcoma

text: Most soft tissue sarcomas arise from what doctors call "sporadic" (or random) genetic mutations within an affected person's cells. Nevertheless, there are certain risk factors associated with an increased risk of developing soft tissue sarcoma. Previous exposure to ionizing radiation is one such risk factor. Exposure to vinyl chloride (e.g., such as the fumes encountered in the production of Polyvinyl chloride (PVC)), Arsenic and Thorotrast all are associated with an increased risk of angiosarcoma. Lymphedema, such as that resulting from certain types of breast cancer treatment, also is a risk factor for development of angiosarcoma. As with bone sarcomas, certain inherited genetic syndromes also are associated with an increased risk of developing soft tissue sarcoma, including Li-Fraumeni syndrome, familial adenomatous polyposis, neurofibromatosis type 1, and heritable RB1 gene mutations. Kaposi's sarcoma is caused by Kaposi's sarcoma-associated herpesvirus (HHV-8).


title: Sarcoma

text: The mechanisms by which healthy cells transform into cancer cells are described in detail elsewhere (see Cancer main page; Carcinogenesis main page). The precise molecular changes that result in sarcoma are not always known, but certain types of sarcomas are associated with particular genetic mutations. Examples include:


title: Sarcoma

text: Diagnosis of bone sarcomas begins with a thorough history and physical examination which may reveal characteristic signs and symptoms (see Signs and Symptoms above). Laboratory studies are not particularly useful in diagnosis, although some bone sarcomas (such as osteosarcoma) may be associated with elevated alkaline phosphatase levels, while others (such as Ewing Sarcoma) can be associated with elevated erythrocyte sedimentation rate. Importantly, however, none of these laboratory findings are specific to bone sarcomas, meaning that elevations in these lab values are associated with many other conditions as well as sarcoma, and thus cannot be relied upon to conclusively diagnose sarcoma. Imaging studies are critically important in diagnosis, and most clinicians will order a plain radiograph (X-ray) initially. Other imaging studies commonly used in diagnosis include magnetic resonance imaging (MRI) studies and radioisotope bone scans. Computed tomography (CT) imaging typically is not used in diagnosis of most types of bone sarcoma, although it is an important tool for staging (see below). Definitive diagnosis requires biopsy of the tumor and careful review of the biopsy specimen by an experienced pathologist.


title: Sarcoma

text: Diagnosis of soft-tissue sarcomas also begins with a thorough history and physical examination. Imaging studies can include either CT or MRI, although CT tends to be preferred for soft tissue sarcomas located in the thorax, abdomen, or retroperitoneum. Positron emission tomography (PET) also may be useful in diagnosis, although its most common use is for staging (see below). As with bone sarcomas, definitive diagnosis requires biopsy of the tumor with evaluation of histology by a trained pathologist.


title: Sarcoma

text: In general, cancer staging refers to how advanced a cancer is, and usually it is based upon factors such as tumor size and whether it has spread to other parts of the body. Staging is important because the stage affects the prognosis (likely outcome), as well as the types of treatments that are likely to be effective against the cancer. With sarcomas, staging requires a determination of whether the tumor has grown into surrounding tissues ("local invasion"), as well as imaging to determine whether it has spread (a process known as "metastasis") to lymph nodes (forming "nodal metastases") or to other tissues or organs in the body (forming "distant metastases").


title: Sarcoma

text: The most common imaging tools used for staging bone sarcomas are MRI or CT to evaluate the primary tumor, contrast-enhanced CT of the chest to evaluate whether the cancer has spread (i.e., metastasized) to the lungs, and radioisotope bone scan to evaluate whether the cancer has spread to other bones. Staging for soft tissue sarcomas typically includes imaging of the primary tumor by MRI or CT to determine tumor size, as well as contrast-enhanced CT of the chest to evaluate for metastatic tumors in the lungs.


title: Sarcoma

text: Like some other cancers, sarcomas are assigned a grade (low, intermediate, or high) based on the appearance of the tumor cells under a microscope. In general, grade refers to how aggressive the cancer is and how likely it is to spread to other parts of the body ("metastasize"). Low-grade sarcomas have a better prognosis than higher-grade sarcomas, and are usually treated surgically, although sometimes radiation therapy or chemotherapy are used. Intermediate- and high-grade sarcomas are more frequently treated with a combination of surgery, chemotherapy, or radiation therapy. Since high-grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for pediatric patients with localized osteosarcoma was only about 20%, but now has risen to 60–70%.


title: Sarcoma

text: In the US, the US Preventive Services Task Force (USPSTF) publishes guidelines recommending preventive screening for certain types of common cancers and other diseases. As of March 2019, the USPSTF does not recommend screening for sarcoma, possibly because it is a very rare type of cancer (see Epidemiology below).


title: Sarcoma

text: The American Cancer Society (ACS) also publishes guidelines recommending preventive screening for certain types of common cancers. Like the USPSTF, as of March 2019 ACS does not recommend preventive screening for sarcoma.


title: Sarcoma

text: The Sarcoma Foundation of America (SFA) is a cancer research organisation. It was founded in 2000 with the main intent of researching possible cures to Sarcoma type Cancers.


title: Sarcoma

text: Surgery is the most common form of the treatment for most sarcomas that have not spread to other parts of the body. Limb-sparing surgery, as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity (arm or leg) sarcoma cases. Additional treatments, including chemotherapy, radiation therapy (also called "radiotherapy") and proton therapy, may be administered "before surgery" (called "neoadjuvant" chemotherapy or radiotherapy) or "after surgery" (called "adjuvant" chemotherapy or radiotherapy). The use of neoadjuvant or adjuvant chemotherapy and radiotherapy significantly improves the prognosis for many sarcoma patients. Treatment can be a long and arduous process, lasting about a year for many patients.


title: Sarcoma

text: In childhood sarcomas, the cytotoxic agent cyclophosphamide is widely used and has shown good anti-tumour efficacy.


title: Sarcoma

text: It is believed that higher doses of chemotherapy might improve survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and can be harmful. Stem cells collected from people before high‐dose chemotherapy can be transplanted back to the person if the blood cell count gets too low; this is called autologous hematopoietic stem cell transplantation. Research to investigate if using high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation was more favourable than standard‐dose chemotherapy found only one RCT and this did not favour either of the two treatment arms with respect to overall survival. Further evidence is needed through well‐designed clinical trials.


title: Sarcoma

text: According to data published by the US National Cancer Institute (NCI), the overall 5-year survival for bone sarcomas is 66.9%. The American Cancer Society (ACS) estimates that 1,660 people in the US will die in 2019 from bone sarcomas, accounting for 0.3% of all cancer deaths. The median age at death is 61 years old, although death can occur in any age group. Thus, 12.3% of bone sarcoma deaths occur in people under 20 years old, 13.8% occur in people 20–34 years old, 5.5% occur in people 35–44 years old, 9.3% occur in people 45–54 years old, 13.5% occur in people 55–64 years old, 16.2% occur in people 65–74 years old, 16.4% occur in people 75–84 years old, and 13.1% occur in people 85 years or older.


title: Sarcoma

text: For soft tissue sarcomas, the overall 5-year survival (irrespective of stage) is 64.5%, but survival is affected by many factors, including stage. Thus, the 5-year survival is 80.8% for soft tissue sarcomas that have not spread beyond the primary tumor ("localized" tumors), 58.0% for soft tissue sarcomas that have spread only to nearby lymph nodes, and 16.4% for soft tissue sarcomas that have spread to distant organs. The ACS estimates that 5,270 people will die from soft tissue sarcoma in 2019, accounting for 0.9% of all cancer deaths.


title: Sarcoma

text: Sarcomas are quite rare. The risk of a previously healthy person receiving a new diagnosis of bone cancer is less than 0.001%, while the risk of receiving a new diagnosis of soft tissue sarcoma is between 0.0014 and 0.005%. The American Cancer Society estimates that in the United States there will be 3,500 new cases of bone sarcoma in 2019, and 12,750 new cases of soft tissue sarcoma. Considering that the total estimated number of new cancer diagnoses (all types of cancer) is 1,762,450, this means bone sarcomas represent only 0.2% of all new cancer diagnoses (making them the 30th most common type of cancer) and soft tissue sarcomas represent only 0.7% (making them the 22nd most common type of cancer) of all new cancer diagnoses in the US in 2019. These estimates are similar to previously reported data.


title: Sarcoma

text: Sarcomas affect people of all ages. Around 50% of bone sarcomas and 20% of soft-tissue sarcomas are diagnosed in people under the age of 35. Some sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children. Most high-grade bone sarcomas, including Ewing's sarcoma and osteosarcoma, are much more common in children and young adults.


title: Sarcoma

text: In 2016, scientists reported the discovery of an osteosarcoma tumor in a 1.6-1.8 million-year-old fossil from the skeleton of the now-extinct hominin species "Australopithecus sediba", making it the earliest-known case of human cancer.


title: Sarcoma

text: Treatment of sarcoma, especially when the sarcoma has spread, or "metastasized", often requires chemotherapy but existing chemotherapeutic medicines are associated with significant toxicities and are not highly effective in killing cancer cells. Therefore, research to identify new medications to treat sarcoma is being conducted . One possibility is the use of cancer immunotherapy (e.g., immune checkpoint inhibitors like anti-PD1, anti-PDL1, and anti-CTLA4 agents) to treat sarcomas. This is not yet an established treatment tool. Other strategies, such as small-molecule targeted therapy, biologic agents (e.g., small interfering RNA molecules), and nanoparticle-directed therapy, also are being investigated.


title: Sarcoma

text: Dr Sameer Rastogi et al. has shown long lasting responses in few sarcomas (UPS & ASPS) on immunotherapy


title: Sarcoma

text: Research to understand the specific genetic and molecular factors that cause sarcoma to develop is underway. This could allow for the design of new targeted therapies and allow physicians to more accurately predict a patient's prognosis.


title: Sarcoma

text: Presence of the H3-B3 immunoregulatory checkpoint receptor in the tumor cells provides the opportunity for clinical trial testing of new drugs and targeted agents and immunotherapies in development.


title: Sarcoma

text: In the US, July is widely recognized as Sarcoma Awareness Month. The UK has a Sarcoma Awareness Week in July led by Sarcoma UK, the bone and soft-tissue cancer charity.


title: Sarcoma

text: American YouTuber Technoblade was diagnosed with sarcoma in August 2021, and died from his illness in June 2022 after the cancer metastasized. He had raised over 500,000$ in a charity stream. Many YouTubers have raised awareness and donated to charities such as the Sarcoma Foundation of America after Technoblade's diagnosis and passing.


title: Pfizer–BioNTech COVID-19 vaccine

text: The Pfizer–BioNTech COVID-19 vaccine (INN: tozinameran), sold under the brand name Comirnaty, is an mRNA-based COVID-19 vaccine developed by the German biotechnology company BioNTech. For its development, BioNTech collaborated with American company Pfizer to carry out clinical trials, logistics, and manufacturing. It is authorized for use in people aged five years and older in some jurisdictions, twelve years and older in some jurisdictions, and for people sixteen years and older in other jurisdictions, to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus. The vaccine is given by intramuscular injection. It is composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. Initial advice indicated that vaccination required two doses given 21 days apart, but the interval was later extended to up to 42 days in the US, and up to four months in Canada.


title: Pfizer–BioNTech COVID-19 vaccine

text: Clinical trials began in April 2020; by November 2020, the vaccine entered phaseIII clinical trials, with over 40,000 people participating. An interim analysis of study data showed a potential efficacy of 91.3% in preventing symptomatic infection within seven days of a second dose and no serious safety concerns. Most side effects are mild to moderate in severity and are gone within a few days. The most common include mild to moderate pain at the injection site, fatigue, and headaches. Reports of serious side effects, such as allergic reactions, are very rare and no long-term complications have been reported.


title: Pfizer–BioNTech COVID-19 vaccine

text: The vaccine is the first COVID19 vaccine to be authorized by a stringent regulatory authority for emergency use and the first cleared for regular use. In December 2020, the United Kingdom was the first country to authorize its use on an emergency basis. It is authorized for use at some level in the majority of countries. On 23 August 2021, the Pfizer–BioNTech vaccine became the first COVID-19 vaccine to be approved in the United States by the Food and Drug Administration (FDA) for those aged sixteen years and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: , more than 1.5billion COVID-19 vaccine doses have been shipped by the company worldwide. As of 30 March 2021, Pfizer and BioNTech aimed to manufacture about 2.5billion doses in 2021. Distribution and storage is a logistical challenge because the vaccine needs to be stored at extremely low temperatures.


title: Pfizer–BioNTech COVID-19 vaccine

text: In August 2022, a bivalent version of the vaccine (Pfizer-BioNTech COVID-19 Vaccine, Bivalent) was authorized for use as a booster dose in individuals twelve years of age and older in the United States. In September 2022, the BA.1 version of the bivalent vaccine (Comirnaty Original/Omicron BA.1 or tozinameran/riltozinameran) was authorized as a booster for use in the United Kingdom for people aged twelve years of age and older. In September 2022, the European Union authorized both the BA.1 and the BA.4/BA.5 booster versions of the bivalent vaccine for people aged twelve years of age and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: The Pfizer–BioNTech COVID-19 vaccine is used to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus, by eliciting an immune response to the S antigen. The vaccine is used to reduce morbidity and mortality from COVID-19.


title: Pfizer–BioNTech COVID-19 vaccine

text: The vaccine is supplied in a multidose vial as "a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection". It must be thawed to room temperature and diluted with normal saline before administration.


title: Pfizer–BioNTech COVID-19 vaccine

text: The initial course consists of two doses. The World Health Organization (WHO) recommends an interval of three to four weeks between doses. Delaying the second dose by up to twelve weeks increases immunogenicity, even in older adults, against all variants of concern. Authors of the Pitch study think that the optimal interval against the Delta variant is around eight weeks, with longer intervals leaving receptors vulnerable between doses.


title: Pfizer–BioNTech COVID-19 vaccine

text: A test-negative case-control study published in August 2021, found that two doses of the BNT162b2 (Pfizer) vaccine had 93.7% effectiveness against symptomatic disease caused by the alpha (B.1.1.7) variant and 88.0% effectiveness against symptomatic disease caused by the delta (B.1.617.2) variant. Notably, effectiveness after one dose of the Pfizer vaccine was 48.7% against alpha and 30.7% against delta, similar to effectiveness provided by one dose of the ChAdOx1 nCoV-19 vaccine.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 27 August, the U.S. Centers for Disease Control and Prevention (CDC) published a study reporting that the effectiveness against infection decreased from to when the Delta variant became predominant in the US, which may be due to unmeasured and residual confounding related to a decline in vaccine effectiveness over time.


title: Pfizer–BioNTech COVID-19 vaccine

text: Unless indicated otherwise, the following effectiveness ratings are indicative of clinical effectiveness two weeks after the second dose. A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval. Effectiveness is generally expected to slowly decrease over time.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 12 November, Public Health England reported a possible but extremely small reduction in effectiveness against symptomatic disease from the Delta sublineage AY.4.2 at longer intervals after the second dose.


title: Pfizer–BioNTech COVID-19 vaccine

text: Preliminary data suggest that the effectiveness against the Omicron variant starts to decline in about 10 weeks, either after the initial two-dose regimen or after the booster dose. For other variants, the effectiveness of the initial doses starts to decline in about six months. A case-control study in Qatar from 1 January to 5 September 2021 found that effectiveness against infection peaked at in the first month after the second dose, followed by a slow decline that accelerated after the fourth month, reaching 20% at months 5 to 7. A similar trajectory was observed against symptomatic disease and against specific variants. Effectiveness against severe disease, hospitalization and death was more robust, peaking at in the second month and remaining almost stable through the sixth month, declining thereafter.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 21 October, a phase 3 trial showed that a booster dose given approximately 11 months after the second dose restored the protective effect to the efficacy level against symptomatic disease from the Delta variant.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 8 December, Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide a similar level of neutralizing antibodies against the Omicron variant as seen after two doses against other variants.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 14 December, private health insurer Discovery Health, in collaboration with the South African Medical Research Council, reported that real-world data from more than 211,000 cases of COVID-19 in South Africa, of which 78,000 were of the Omicron variant, indicate that effectiveness against the variant after two doses is about 70% against hospital admission and 33% against symptomatic disease. Protection against hospital admission is maintained for all ages and groups with comorbidities.


title: Pfizer–BioNTech COVID-19 vaccine

text: Based on the results of a preliminary study, the U.S. Centers for Disease Control and Prevention (CDC) recommends that pregnant women get vaccinated with the COVID19 vaccine.


title: Pfizer–BioNTech COVID-19 vaccine

text: A statement by the British Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) reported that the two agencies had reached a conclusion that the vaccine is safe and effective in children aged between 12 and 15 years.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 19 May 2021, experts commissioned by the Norwegian Medicines Agency concluded that the Pfizer-BioNTech vaccine is the likely cause of ten deaths of frail elderly patients in Norwegian nursing homes. They said that people with very short life expectancies have little to gain from vaccination, having a real risk of adverse reactions in the last days of life and of dying earlier.


title: Pfizer–BioNTech COVID-19 vaccine

text: A 2021 report by the New South Wales Government (NSW Health) in Australia found that the Pfizer-BioNTech vaccine is safe for those with various forms of immunodeficiency or immunosuppression, though it does note that the data on said groups is limited, due to their exclusion from many of the vaccine earlier trials held in 2020. It notes that the World Health Organization advises that the vaccine is among the three COVID-19 vaccines (alongside that of Moderna and AstraZeneca) it deems safe to give to immunocompromised individuals, and that expert consensus generally recommends their vaccination. The report states that the vaccines were able to generate an immune response in those individuals, though it does also note that this response is weaker than in those that are not immunocompromised. It recommends that specific patient groups, such as those with cancer, inflammatory bowel disease and various liver diseases be prioritised in the vaccination schedules over other patients that do not have said conditions.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 20 September 2021, Pfizer announced that a clinical trial conducted in more than 2,200 children aged 5–11 has generated a "robust" response and is safe.


title: Pfizer–BioNTech COVID-19 vaccine

text: In large phase 3 trials for the vaccine there were no reported serious safety findings, and it observed low incidence of serious adverse events.


title: Pfizer–BioNTech COVID-19 vaccine

text: Most side effects of the Pfizer–BioNTech COVID19 vaccine are mild to moderate in severity and are gone within a few days. They are similar to other adult vaccines and are normal signs that the body is building protection to the virus. During clinical trials, the common side effects affecting more than 1 in 10 people are (in order of frequency): pain and swelling at the injection site, tiredness, headache, muscle aches, chills, joint pain, and fever. Fever is more common after the second dose.


title: Pfizer–BioNTech COVID-19 vaccine

text: The European Medicines Agency (EMA) regularly reviews the data on the vaccine's safety. The safety report published on 8 September 2021, by the EMA was based on over 392million doses administered in the European Union. According to the EMA "the benefits of Comirnaty in preventing COVID19 continue to outweigh any risks, and there are no recommended changes regarding the use of this vaccine." Rare side effects (that may affect up to 1 in 1,000 people) include temporary one sided facial drooping and allergic reactions such as hives or swelling of the face.


title: Pfizer–BioNTech COVID-19 vaccine

text: Documented hypersensitivity to polyethylene glycol (PEG) (a very rare allergy) is listed as a contraindication to the COVID-19 Pfizer vaccine. Severe allergic reaction has been observed in approximately eleven cases per million doses of vaccine administered. According to a report by the US Centers for Disease Control and Prevention, 71% of those allergic reactions happened within 15 minutes of vaccination and mostly (81%) among people with a documented history of allergies or allergic reactions. The UK's Medicines and Healthcare products Regulatory Agency (MHRA) advised on 9December 2020 that people who have a history of "significant" allergic reaction should not receive the Pfizer–BioNTech COVID19 vaccine. On 12 December, the Canadian regulator followed suit, noting that: "Both individuals in the U.K. had a history of severe allergic reactions and carried adrenaline auto injectors. They both were treated and have recovered."


title: Pfizer–BioNTech COVID-19 vaccine

text: In June 2021, the Israel's Ministry of Health announced a probable relationship between the second dose and myocarditis in a small group of 16–30-year-old men. Between December 2020 and May 2021, there were 55 cases of myocarditis per 1million people vaccinated, 95% of which were classified as mild and most spent no more than four days in the hospital. Since April 2021, increasing number of cases of myocarditis and pericarditis have been reported in the United States in about 13 per 1million young people, mostly male and over the age of 16, after vaccination with the Pfizer–BioNTech or the Moderna vaccine. Most affected individuals recover quickly with adequate treatment and rest. Since February 2022, the German Standing Committee on Vaccination recommends aspiration for COVID-19 vaccination as precautionary measure.


title: Pfizer–BioNTech COVID-19 vaccine

text: The BioNTech technology for the BNT162b2 vaccine is based on use of nucleoside-modified mRNA (modRNA) which encodes a mutated form of the full-length spike protein found on the surface of the SARS-CoV-2 virus, triggering an immune response against infection by the virus protein.


title: Pfizer–BioNTech COVID-19 vaccine

text: The modRNA sequence of the vaccine is 4,284 nucleotides long. It consists of a five-prime cap; a five prime untranslated region derived from the sequence of human alpha globin; a signal peptide (bases 55–102) and two proline substitutions (K986P and V987P, designated "2P") that cause the spike to adopt a prefusion-stabilized conformation reducing the membrane fusion ability, increasing expression and stimulating neutralizing antibodies; a codon-optimized gene of the full-length spike protein of SARS-CoV-2 (bases 103–3879); followed by a three prime untranslated region (bases 3880–4174) combined from "AES" and mtRNR1 selected for increased protein expression and mRNA stability and a poly(A) tail comprising 30 adenosine residues, a 10-nucleotide linker sequence, and 70 other adenosine residues (bases 4175–4284). The sequence contains no uridine residues; they are replaced by 1-methyl-3'-pseudouridylyl. The 2P proline substitutions in the spike proteins were originally developed for a Middle East respiratory syndrome (MERS) vaccine by researchers at the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, Scripps Research, and Jason McLellan's team (at the University of Texas at Austin, previously at Dartmouth College).


title: Pfizer–BioNTech COVID-19 vaccine

text: In addition to the mRNA molecule, the vaccine contains the following inactive ingredients (excipients):


title: Pfizer–BioNTech COVID-19 vaccine

text: The first four of these are lipids. The lipids and modRNA together form nanoparticles that act not only as carriers to get the modRNA into the human cells, but also as adjuvants. ALC-0159 is a polyethylene glycol conjugate, i.e., a PEGylated lipid.


title: Pfizer–BioNTech COVID-19 vaccine

text: Pfizer and BioNTech are manufacturing the vaccine in their own facilities in the United States and in Europe. The license to distribute and manufacture the vaccine in China was purchased by Fosun, alongside its investment in BioNTech.


title: Pfizer–BioNTech COVID-19 vaccine

text: Manufacturing the vaccine requires a three-stage process. The first stage involves the molecular cloning of DNA plasmids that code for the spike protein by infusing them into "Escherichia coli" bacteria. For all markets, this stage is conducted in the United States, at a small Pfizer pilot plant in Chesterfield, Missouri (near St. Louis). After four days of growth, the bacteria are killed and broken open, and the contents of their cells are purified over a week and a half to recover the desired DNA product. The DNA is bottled and frozen for shipment. Safely and quickly transporting the DNA at this stage is so important that Pfizer has used its company jet and helicopter to assist.


title: Pfizer–BioNTech COVID-19 vaccine

text: The second stage is being conducted at a Pfizer plant in Andover, Massachusetts, in the United States, and at BioNTech's plants in Germany. The DNA is used as a template to build the desired mRNA strands, which takes about four days. Once the mRNA has been created and purified, it is frozen in plastic bags about the size of a large shopping bag, of which each can hold up to 10million doses. The bags are placed on trucks which take them to the next plant.


title: Pfizer–BioNTech COVID-19 vaccine

text: The third stage is being conducted at Pfizer plants in Portage, Michigan (near Kalamazoo) in the United States, and Puurs in Belgium. This stage involves combining the mRNA with lipid nanoparticles, then filling vials, boxing vials, and freezing them. Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids. As of November 2020, the major bottleneck in the manufacturing process is combining mRNA with lipid nanoparticles. At this stage, it takes only four days to go from mRNA and lipids to finished vials, but each lot must then spend several weeks in deep-freeze storage while undergoing verification against 40 quality-control measures.


title: Pfizer–BioNTech COVID-19 vaccine

text: Before May 2021, the Pfizer plant in Puurs was responsible for all vials for destinations outside the United States. Therefore, all doses administered in the Americas outside of the United States before that point in time required at least two transatlantic flights (one to take DNA to Europe and one to bring back finished vaccine vials).


title: Pfizer–BioNTech COVID-19 vaccine

text: In February 2021, BioNTech announced it would increase production by more than 50% to manufacture 2billion doses in 2021, raised again at the end of March to 2.5billion doses in 2021.


title: Pfizer–BioNTech COVID-19 vaccine

text: In February 2021, Pfizer revealed that the entire sequence initially took about 110 days on average from start to finish, and that the company is making progress on reducing the time to 60 days. More than half the days in the production process are dedicated to rigorous testing and quality assurance at each of the three stages. Pfizer also revealed that the process requires 280 components and relies upon 25 suppliers located in 19 countries.


title: Pfizer–BioNTech COVID-19 vaccine

text: Vaccine manufacturers normally take several years to optimize the process of making a particular vaccine for speed and cost-effectiveness before attempting large-scale production. Due to the urgency presented by the COVID19 pandemic, Pfizer and BioNTech began production immediately with the process by which the vaccine had been originally formulated in the laboratory, then started to identify ways to safely speed up and scale up that process.BioNTech announced in September 2020, that it had signed an agreement to acquire a manufacturing facility in Marburg, Germany, from Novartis to expand their vaccine production capacity. Once fully operational, the facility would produce up to 750million doses per year, or more than 60million doses per month. The site will be the third BioNTech facility in Europe that produces the vaccine, while Pfizer operates at least four production sites in the United States and Europe.


title: Pfizer–BioNTech COVID-19 vaccine

text: The Marburg facility had previously specialized in cancer immunotherapy for Novartis. By the end of March 2021, BioNTech had finished retrofitting the facility for mRNA vaccine production and retraining its 300 staff, and obtained approval to begin manufacturing. Besides making mRNA, the Marburg facility also performs the step of combining mRNA with lipids to form lipid nanoparticles, then ships the vaccine in bulk to other facilities for fill and finish (i.e., filling and boxing vials).


title: Pfizer–BioNTech COVID-19 vaccine

text: On 23 April 2021, the EMA authorized an increase in batch size and associated process scale up at Pfizer's plant in Puurs. This increase is expected to have a significant impact on the supply of the vaccine in the European Union.


title: Pfizer–BioNTech COVID-19 vaccine

text: At the end of April 2021, it was reported that Pfizer had started to export vaccine doses to Mexico and Canada from the Kalamazoo plant, which is much closer geographically to both countries than the Puurs plant.


title: Pfizer–BioNTech COVID-19 vaccine

text: The vaccine is delivered in vials that, once diluted, contain 2.25 mL of vaccine, comprising 0.45 mL frozen and 1.8 mL diluent. According to the vial labels, each vial contains five 0.3 mL doses, however excess vaccine may be used for one, or possibly two, additional doses. The use of low dead space syringes to obtain the additional doses is preferable, and partial doses within a vial should be discarded. The Italian Medicines Agency officially authorized the use of excess doses remaining within single vials. The Danish Health Authority allows mixing partial doses from two vials. As of 8January 2021, each vial contains six doses. In the United States, vials will be counted as five doses when accompanied by regular syringes and as six doses when accompanied by low dead space syringes.The vaccine can be stored at for thirty days before use and at or for up to two hours before use. During distribution the vaccine is stored in special containers that maintain temperatures between .


title: Pfizer–BioNTech COVID-19 vaccine

text: Low-income countries have limited cold chain capacity for ultracold transport and storage of a vaccine. The necessary storage temperatures for the vaccine are much lower than for the similar Moderna vaccine. The head of Indonesia's Bio Farma Honesti Basyir said purchasing the vaccine is out of the question for the world's fourth-most populous country, given that it did not have the necessary cold chain capability. Similarly, India's existing cold chain network can handle only temperatures between , far above the requirements of the vaccine.


title: Pfizer–BioNTech COVID-19 vaccine

text: Before COVID19 vaccines, a vaccine for an infectious disease had never before been produced in less than several years, and no vaccine existed for preventing a coronavirus infection in humans. The SARS-CoV-2 virus, which causes COVID19, was detected in December 2019, and BioNTech began development of a COVID19 vaccine on 10 January 2020, when the SARS-CoV-2 genetic sequences were released by the Chinese Center for Disease Control and Prevention via GISAID, triggering an urgent international response to prepare for an outbreak and hasten development of preventive vaccines.


title: Pfizer–BioNTech COVID-19 vaccine

text: The vaccine's development began when BioNTech founder Uğur Şahin read an article in the medical journal "The Lancet" that convinced him the COVID19 coronavirus in China would soon become a global pandemic, so he called for scientists at the company to cancel their vacations and start development of a COVID19 vaccine in January 2020. BioNTech started its program 'Project Lightspeed' to develop a vaccine against the new COVID19 virus based on its already established mRNA-technology, which they had been developing since leading mRNA researcher Katalin Karikó joined the company in 2013. Several variants of the vaccine were created in their laboratories in Mainz, and 20 of those were presented to experts of the Paul Ehrlich Institute in Langen.


title: Pfizer–BioNTech COVID-19 vaccine

text: Meanwhile, since 2018, Pfizer had been working with BioNTech on developing a mRNA vaccine for influenza, but the chief executive officers of the two companies did not become personally acquainted until COVID-19 came along. After a few phone calls, Pfizer CEO Albert Bourla and Şahin agreed that their companies would work together on the development of BioNTech's COVID-19 vaccine. To the horror of Pfizer's lawyers, the two agreed to begin work immediately, because time was of the essence, with no formal written legal agreement in place to govern the new collaboration. BioNTech transferred its know-how to Pfizer the next day. A letter of intent was signed three weeks later, and the formal commercial agreement between Pfizer and BioNTech for the COVID-19 vaccine was signed in January 2021.


title: Pfizer–BioNTech COVID-19 vaccine

text: BioNTech received a investment from Fosun in March 2020, in exchange for 1.58million shares in BioNTech and the future development and marketing rights of BNT162b2 in China.


title: Pfizer–BioNTech COVID-19 vaccine

text: In April 2020, BioNTech signed a partnership with Pfizer and received $185million, including an equity investment of approximately $113million.


title: Pfizer–BioNTech COVID-19 vaccine

text: In June 2020, BioNTech received () in financing from the European Commission and European Investment Bank. The Bank's deal with BioNTech started early in the pandemic, when the Bank's staff reviewed its portfolio and came up with BioNTech as one of the companies capable of developing a COVID19 vaccine. The European Investment Bank had already signed a first transaction with BioNTech in 2019.


title: Pfizer–BioNTech COVID-19 vaccine

text: In September 2020, the German government granted BioNTech () for its COVID19 vaccine development program.


title: Pfizer–BioNTech COVID-19 vaccine

text: Pfizer CEO Albert Bourla said he decided against taking funding from the US government's Operation Warp Speed for the development of the vaccine "because I wanted to liberate our scientists [from] any bureaucracy that comes with having to give reports and agree how we are going to spend the money in parallel or together, etc." Pfizer did enter into an agreement with the US for the eventual distribution of the vaccine, as with other countries.


title: Pfizer–BioNTech COVID-19 vaccine

text: PhaseI–II Trials were started in Germany on 23 April 2020, and in the U.S. on 4May 2020, with four vaccine candidates entering clinical testing. The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech. Before choosing BNT162b2, BioNTech and Pfizer had conducted phaseI trials on BNT162b1 in Germany and the United States, while Fosun performed a PhaseI trial in China. In these PhaseI studies, BNT162b2 was shown to have a better safety profile than the other three BioNTech candidates.


title: Pfizer–BioNTech COVID-19 vaccine

text: The Pivotal PhaseII–III Trial with the lead vaccine candidate "BNT162b2" began in July. Preliminary results from PhaseI–II clinical trials on BNT162b2, published in October 2020, indicated potential for its safety and efficacy. During the same month, the European Medicines Agency (EMA) began a periodic review of BNT162b2.


title: Pfizer–BioNTech COVID-19 vaccine

text: The study of BNT162b2 is a continuous-phase trial in phaseIII as of November 2020. It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals". The study expanded during mid-2020 to assess efficacy and safety of BNT162b2 in greater numbers of participants, reaching tens of thousands of people receiving test vaccinations in multiple countries in collaboration with Pfizer and Fosun.


title: Pfizer–BioNTech COVID-19 vaccine

text: The phase III trial assesses the safety, efficacy, tolerability, and immunogenicity of BNT162b2 at a mid-dose level (two injections separated by 21 days) in three age groups: 12–15 years, 16–55 years or above 55 years. The PhaseIII results indicating a 95% efficacy of the developed vaccine were published on 18 November 2020. For approval in the EU, an overall vaccine efficacy of 95% was confirmed by the EMA. The EMA clarified that the second dose should be administered three weeks after the first dose.


title: Pfizer–BioNTech COVID-19 vaccine

text: At 14 days after dose 1, the cumulative incidence begins to diverge between the vaccinated group and the placebo group. The highest concentration of neutralizing antibodies is reached 7 days after dose 2 in younger adults and 14 days after dose 2 in older adults.


title: Pfizer–BioNTech COVID-19 vaccine

text: The ongoing phase III trial, which is scheduled to run from 2020 to 2022, is designed to assess the ability of BNT162b2 to prevent severe infection, as well as the duration of immune effect.


title: Pfizer–BioNTech COVID-19 vaccine

text: High antibody activity persists for at least three months after the second dose, with an estimated antibody half-life of 55 days. From these data, one study suggested that antibodies might remain detectable for around 554 days.


title: Pfizer–BioNTech COVID-19 vaccine

text: Pfizer and BioNTech started a PhaseII–III randomized control trial in healthy pregnant women 18 years of age and older (NCT04754594). The study will evaluate 30mcg of BNT162b2 or placebo administered via intramuscular injection in two doses, 21 days apart. The PhaseII portion of the study will include approximately 350 pregnant women randomized 1:1 to receive BNT162b2 or placebo at 27 to 34 weeks' gestation. The PhaseIII portion of this study will assess the safety, tolerability, and immunogenicity of BNT162b2 or placebo among pregnant women enrolled at 24 to 34 weeks' gestation. Pfizer and BioNTech announced on 18 February 2021 that the first participants received their first dose in this trial.


title: Pfizer–BioNTech COVID-19 vaccine

text: A study published in March 2021, in the "American Journal of Obstetrics and Gynecology" came to the conclusion that messenger RNA vaccines against the novel coronavirus, such as the Pfizer-BioNTech and Moderna vaccines were safe and effective at providing immunity against infection to pregnant and breastfeeding mothers. Furthermore, they found that naturally occurring antibodies created by the mother's immune system were passed on to their children via the placenta and/or breastmilk, thus resulting in passive immunity among the child, effectively giving the child protection against the disease. The study also found that vaccine-induced immunity among the study's participants was stronger in a statistically significant way over immunity gained through recovery from a natural COVID19 infection. In addition, the study reported that the occurrence and intensity of potential side effects in those undergoing pregnancy or lactating was very similar to those expected from non-pregnant populations, remaining generally very minor and well tolerated, mostly including injection site soreness, minor headaches, muscles aches or fatigue for a short period of time.


title: Pfizer–BioNTech COVID-19 vaccine

text: In January 2021, Pfizer said it had finished enrolling 2,259 children aged between 12 and 15 years to study the vaccine's safety and efficacy.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 31 March 2021, Pfizer and BioNTech announced from initial PhaseIII trial data that the vaccine is 100% effective for those aged 12 to 15 years of age, with trials for those younger still in progress.


title: Pfizer–BioNTech COVID-19 vaccine

text: A research letter published in "JAMA" reported that the vaccines appeared to be safe for immunosuppressed organ transplant recipients, but that the resulting antibody response was considerably poorer than in the non-immunocompromised population after only one dose. The paper admitted the limitation of only reviewing the data following the first dose of a two-dose cycle vaccine.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 2 November 2021, "The BMJ" published a piece by journalist Paul D. Thacker alleging there has been "poor practice" at Ventavia, one of the companies involved in the phase III evaluation trials of the Pfizer vaccine. The report was enthusiastically embraced by anti-vaccination activists. David Gorski commented in "Science-Based Medicine" that Thacker's article presented facts without necessary context to misleading effect, playing up the seriousness of the noted problems.


title: Pfizer–BioNTech COVID-19 vaccine

text: Although jointly developed with Pfizer, Comirnaty is based on BioNTech's proprietary mRNA technology, and BioNTech holds the Marketing Authorization in the United States, the European Union, the UK, and Canada; expedited licenses such as the US emergency use authorization (EUA) are held jointly with Pfizer in many countries.


title: Pfizer–BioNTech COVID-19 vaccine

text: The United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave the vaccine "rapid temporary regulatory approval to address significant public health issues such as a pandemic" on 2December 2020, which it is permitted to do under the Medicines Act 1968. It is the first COVID19 vaccine to be approved for national use after undergoing large scale trials, and the first mRNA vaccine to be authorized for use in humans. The United Kingdom thus became the first Western country to approve a COVID19 vaccine for national use, although the decision to fast-track the vaccine was criticized by some experts.


title: Pfizer–BioNTech COVID-19 vaccine

text: After the United Kingdom, the following countries and regions expedited processes to approve the Pfizer–BioNTech COVID19 vaccine for use: Argentina, Australia, Bahrain, Canada, Chile, Costa Rica, Ecuador, Hong Kong, Iraq, Israel, Jordan, Kuwait, Malaysia, Mexico, Oman, Panama, the Philippines, Qatar, Saudi Arabia, Singapore, South Korea, the United Arab Emirates, the United States, and Vietnam.


title: Pfizer–BioNTech COVID-19 vaccine

text: In the United States, an emergency use authorization (EUA) is "a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID19 pandemic", according to the Food and Drug Administration (FDA). Pfizer applied for an EUA on 20 November 2020, and the FDA approved the application three weeks later on 11 December 2020. The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) approved recommendations for vaccination of those aged sixteen years or older. Following the EUA issuance, BioNTech and Pfizer continued the PhaseIII clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) of the vaccine in the United States. On 10 May 2021, the US FDA also authorized the vaccine for people aged 12 to 15 under an expanded EUA. The FDA recommendation was endorsed by the ACIP and adopted by the CDC on 12 May 2021. In October 2021, the EUA was expanded to include children aged 5 through 11 years of age. In June 2022, the EUA was expanded to include children aged six months through four years of age.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 16 February 2021, the South African Health Products Regulatory Authority (SAHPRA) in South Africa issued Section 21, Emergency Use Approval for the vaccine.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 5 May 2021, Health Canada authorized the vaccine for people aged 12 to 15. On 18 May 2021, Singapore's Health Sciences Authority authorized the vaccine for people aged 12 to 15. The European Medicines Agency (EMA) followed suit on 28 May 2021.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 4 June 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) came to a similar decision and approved the use of the vaccine for people twelve years of age and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 19 December 2020, the Swiss Agency for Therapeutic Products (Swissmedic) granted temporary authorization for the Pfizer–BioNTech COVID19 vaccine for regular use, two months after receiving the application, saying the vaccine fully complied with the requirements of safety, efficacy and quality. This is the first authorization under a standard procedure.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 21 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended granting conditional marketing authorization for the Pfizer–BioNTech COVID19 vaccine under the brand name Comirnaty. The recommendation was accepted by the European Commission the same day.


title: Pfizer–BioNTech COVID-19 vaccine

text: On 23 February 2021, the Brazilian Health Regulatory Agency approved the Pfizer–BioNTech COVID19 vaccine under its standard marketing authorization procedure. In June 2021, the approval was extended to those aged twelve or over. Pfizer's negotiation process with Brazil (and other Latin American countries) was described as "bullying". The contract prohibits the state of Brazil from publicly discussing the existence or the terms of their agreement with Pfizer–BioNTech without the former's written consent. Brazil was also restricted from donating or receiving donations of vaccines.


title: Pfizer–BioNTech COVID-19 vaccine

text: In July 2021, the U.S. Food and Drug Administration (FDA) granted priority review designation for the biologics license application (BLA) for the Pfizer–BioNTech COVID-19 vaccine with a goal date for the decision in January 2022. On 23 August 2021, the FDA approved the vaccine for use for those aged sixteen years and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: The Pfizer-BioNTech Comirnaty COVID-19 vaccine was authorized in Canada on 16 September 2021, for people aged twelve and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: In September 2022, the CHMP of the EMA recommended converting the conditional marketing authorizations of the vaccine into standard marketing authorizations. The recommendation covers all existing and upcoming adapted Comirnaty vaccines, including the adapted Comirnaty Original/Omicron BA.1 (tozinameran/riltozinameran) and Comirnaty Original/Omicron BA.4/5 (tozinameran/famtozinameran).


title: Pfizer–BioNTech COVID-19 vaccine

text: On 29 July 2021, Israel's Prime Minister announced that the country was rolling out a third dose of the Pfizer-BioNTech vaccine to people over the age of 60, based on data that suggested significant waning immunity from infection over time for those with two doses. The country expanded the availability to all Israelis over the age of 12, after five months since their second shot. On 29 August 2021, Israel's coronavirus czar announced that Israelis who had not received a booster shot within six months of their second dose would lose access to the country's green pass vaccine passport. Studies performed in Israel found that a third dose reduced the incidence of serious illness.<ref name="doi 10.1056/nejmoa2114255"></ref>


title: Pfizer–BioNTech COVID-19 vaccine

text: On 18 August 2021, the United States Department of Health and Human Services (HHS) announced a plan to offer a booster dose eight months after the second dose, citing evidence of reduced protection against mild and moderate disease and the possibility of reduced protection against severe disease, hospitalization, and death. The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) authorized the use of an additional mRNA vaccine dose for immunocompromised individuals at that time. Scientists and the WHO noted in August 2021, the lack of evidence on the need for a booster dose for healthy people and that the vaccine remains effective against severe disease months after administration. In a statement, the WHO and Strategic Advisory Group of Experts (SAGE) said that, while protection against infection may be diminished, protection against severe disease will likely be retained due to cell-mediated immunity. Research into optimal timing for boosters is ongoing, and a booster too early may lead to less robust protection.


title: Pfizer–BioNTech COVID-19 vaccine

text: In September 2021, the FDA and CDC authorizations were extended to provide a third shot for other specific groups.


title: Pfizer–BioNTech COVID-19 vaccine

text: In October 2021, the European Medicines Agency (EMA) stated that a booster shot of the vaccine could be given to healthy people, aged 18 years and older, at least six months after their second dose. It also stated that people with "severely weakened" immune systems can receive an extra dose of either the Pfizer-BioNTech vaccine or the Moderna vaccine starting at least 28 days after their second dose. The final approval to provide booster shots in the European Union will be decided by each national government.


title: Pfizer–BioNTech COVID-19 vaccine

text: In October 2021, the FDA and the CDC authorized the use of either homologous or heterologous vaccine booster doses.


title: Pfizer–BioNTech COVID-19 vaccine

text: In October 2021, the Australian Therapeutic Goods Administration (TGA) provisionally approved a booster dose of Comirnaty for people 18 years of age and older.


title: Pfizer–BioNTech COVID-19 vaccine

text: In January 2022, the FDA expanded the emergency use authorization to provide for the use of a vaccine booster dose to those aged 12 through 15 years of age, and it shortened the waiting period after primary vaccination to five months from six months.