Tozinameran[12] (INN), codenamed BNT162b2, and commonly known as the Pfizer–BioNTech COVID-19 vaccine, is a COVID-19 vaccine developed by BioNTech in cooperation with Pfizer. It is both the first COVID-19 vaccine to be authorized by a stringent regulatory authority for emergency use[13][14] and the first cleared for regular use.[11]
It is given by intramuscular injection. It is an RNA vaccine composed of nucleoside-modified mRNA (modRNA) encoding a mutated form of the spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles.[15][16] The vaccination requires two doses given three weeks apart.[17][18][19] Its ability to prevent severe infection in children, pregnant women, or immune-compromised people is unknown, as is the duration of the immune effect it confers.[19][20][21]
Trials began in April 2020; by November, the vaccine had been tested on more than 40,000 people.[22] An interim analysis of study data showed a potential efficacy of over 90% in preventing infection within seven days of a second dose.[18][19] The most common side effects include mild to moderate pain at the injection site, fatigue, and headache.[23][24] As of December 2020, reports of serious side effects, such as allergic reactions, have been very rare,[a] and no long-term complications have been reported.[26]
In December 2020, tozinameran was under evaluation for emergency use authorization (EUA) for widespread use by several medical regulators globally. Emergency authorization is required as its Phase III clinical trials are still ongoing: monitoring of the primary outcomes will continue until August 2021, while monitoring of the secondary outcomes will continue until January 2023.[17] The United Kingdom was the first country to authorize its use on an emergency basis.[26] Other countries followed within a week.[5][27][28] By 16 December, 138,000 people in Britain had received the vaccine as part of the national vaccination programme.[29]
BioNTech is the initial developer of the vaccine, which partnered with Pfizer for the developing, logistics, finances, overseeing the clinical trials, and for worldwide manufacturing, with the exception of China where the license to distribute and manufacture was purchased by Fosun, alongside its investment in BioNTech.[30][31] Distribution to Germany and Turkey (likely due to origins of BioNTech's founders) is by BioNTech itself.[32] Pfizer indicated in November 2020, that 50 million doses could be available globally by the end of 2020, with about 1.3 billion doses in 2021.[19] Pfizer has advanced purchase agreements of about US$3 billion for providing a licensed vaccine in the United States, European Union, United Kingdom, Japan, Canada, Peru, and Mexico.[33] Distribution and storage of the vaccine is a global logistics challenge because it needs to be stored at temperatures between −80 and −60 °C (−112 and −76 °F),[34] until hours before vaccination.[33][34]
Contents
Development and funding
A vaccine for an infectious disease has never before been produced in less than several years, and no vaccine exists for preventing a coronavirus infection in humans.[35] After the coronavirus was detected in December 2019,[36] the genetic sequence of COVID‑19 was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive vaccine.[37][38] In January 2020, German biotech-company BioNtech started its program 'Lightspeed' to develop a vaccine against the new COVID-19 virus based on its already established mRNA-technology.[22] 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.[39] Phase I / II Trials were started in Germany on 23 April 2020, and in the U.S. on 4 May 2020, with four vaccine candidates entering clinical testing. The Initial Pivotal Phase II / III Trial with the lead vaccine candidate 'BNT162b2' began in July. The Phase III results indicating a 95% effectiveness of the developed vaccine were published on 18 November 2020.[22]
BioNTech received a US$135 million investment from Fosun in March 2020 in exchange for 1.58 million shares in BioNTech and the future development and marketing rights of BNT162b2 in China,[31] Hong Kong, Macau and Taiwan.[40]
In September 2020, the German government granted BioNTech €375 million (US$445 million) for its COVID-19 vaccine development program at a time when Pfizer funded its portion of development costs without government funding.[41] BioNTech had also received €100 million (US$119 million) in financing from the European Commission and European Investment Bank, with the funding agreement finalized in June 2020.[42]
Pfizer CEO Albert Bourla stated that 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.[43]
Vaccine technology
See also: RNA vaccine and COVID-19 vaccine § Technology platforms
The BioNTech technology for the BNT162b2 vaccine is based on use of nucleoside-modified mRNA (modRNA) which encodes part of the spike protein found on the surface of the SARS-CoV-2 coronavirus (COVID-19), triggering an immune response against infection by the virus protein.[44]
The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech.[17][44][45] Prior to choosing BNT162b2, BioNTech and Pfizer had conducted Phase I trials on BNT162b1 in Germany and the United States, while Fosun performed a Phase I trial in China.[16][46] In these Phase I studies, BNT162b2 was shown to have a better safety profile than the other three BioNTech candidates.[46]
Sequence
The modRNA sequence of tozinameran is 4,284 nucleotides long, with a molecular weight of approximately 1388 kDa.[47][48] It consists of a five-prime cap; a five prime untranslated region derived from the sequence of human alpha globin; a signal peptide coding region (bases 55–102); an optimized sequence which encodes a mutated version of the spike protein of SARS-CoV-2, containing two proline substitutions (K986P and V987P, designated "2P") that cause it to adopt a shape that stimulates neutralizing antibodies (bases 103-3879);[15][49] the three prime untranslated region (bases 3880–4174); and a poly(A) tail comprising 30 adenosine residues, a 10-nucleotide linker sequence, and 70 other adenosine residues (bases 4175-4284).[48] The sequence contains no uridine residues; it is replaced by 1-methyl-3′-pseudouridine.[48]
Composition
The vaccine contains the following inactive ingredients (excipients):[50][3]
ALC-0315 = ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)
ALC-0159 = 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
cholesterol
dibasic sodium phosphate dihydrate
monobasic potassium phosphate
potassium chloride
sodium chloride
sucrose
water for injection
The first four of these are lipids. The lipids and modRNA together form nanoparticles. ALC-0159 is a polyethylene glycol conjugate (that is, a PEGylated lipid).[51]
The vaccine is supplied in a multidose vial as "a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection".[8][9] It must be thawed to room temperature and diluted with normal saline before administration.[9]
Clinical research
See also: COVID-19 vaccine § Clinical trials started in 2020
Preliminary results from Phase I–II clinical trials on BNT162b2, published in October 2020, indicated potential for its efficacy and safety.[15][45] During the same month, the European Medicines Agency (EMA) began a periodic review of BNT162b2.[52]
The study of BNT162b2 is a continuous-phase trial in Phase III as of November 2020.[17] It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals".[17] The early-stage research on BNT162b2 determined the safety and dose level for two vaccine candidates, with the trial expanding 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.[19][31]
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.[17]
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.[19][20][21] Side effects include serious allergic reaction in those susceptible,[53] aches and fever.[19]
Authorizations
Expedited
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 2 December 2020, which it is permitted to do under the 1968 Medicines Act.[54] It was the first COVID-19 vaccine to be approved for national use after undergoing large scale trials,[55] and the first mRNA vaccine to be authorized for use in humans.[13][56] The United Kingdom thus became the first Western country to approve a COVID-19 vaccine for national use,[57] although the decision to fast-track the vaccine was criticised by some experts.[58] On 8 December 2020, Margaret "Maggie" Keenan, 90, from Fermanagh, became the first person to receive the vaccine in the UK.[59] By 16 December, 138,000 British residents had received the vaccine as part of the national vaccination programme.[29]
In December, after the United Kingdom, the following countries expedited processes to approve the Pfizer-BioNTech COVID-19 vaccine for use: Bahrain,[60] Canada,[61][62] Mexico,[63] the United States,[7] Kuwait,[64] Singapore,[65] Jordan,[66] Oman,[67] Saudi Arabia, Ecuador, and Chile.[68][69][28]
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 COVID-19 pandemic", according to the FDA.[70] Following an EUA issuance, BioNTech-Pfizer are expected to continue the Phase III clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) of the vaccine in the United States.[70][71][72] The United States Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) approved recommendations for vaccination of those aged 16 years or older.[73][74]
Standard
On 19 December 2020, the Swiss Agency for Therapeutic Products (Swissmedic) approved the Pfizer-BioNTech COVID-19 vaccine for regular use, two months after receiving the application, stating that the vaccine fully complied with the requirements of safety, efficacy and quality. This is the first authorization under a standard procedure, as Swiss laws do not allow emergency approvals.[1][75]
On December 21, 2020, the European Medicines Agency (EMA) recommended granting conditional marketing authorization for tozinameran.[76][2] The recommendation was accepted by the European Commission shortly thereafter, with EMA director Emer Cooke confirming that despite the "conditional" qualifier, the vaccine was granted full authorization rather than for emergency or temporary use.[77]
Adverse events
As a result of two vaccinees who had severe anaphylactic reactions, the UK's MHRA advised on 9 December 2020 that people who have a history of "significant" allergic reaction should not receive the Pfizer-BioNTech COVID-19 vaccine.[78][79][80] 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."[50]
As of 18 December, the US CDC stated that in their jurisdiction six cases of "severe allergic reaction" had been recorded from more than 250,000 vaccinations, and of those six only one person had a "history of vaccination reactions".[81]
Manufacturing
Pfizer is manufacturing the vaccine in its own facilities in a three-stage process. The first stage, conducted at a small pilot plant in St. Louis, involves the molecular cloning of DNA plasmids that code for the spike protein by infusing them into Escherichia coli bacteria. 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 stored in tiny bottles 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.[82]
The second stage is being conducted at plants in Andover, Massachusetts, and in Germany. The DNA is used as a template to build the desired mRNA strands. 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 5 to 10 million doses. The bags are placed on special racks on trucks which take them to the next plant.[82]
The third stage is being conducted at plants in Kalamazoo, Michigan, and Puurs, Belgium. This stage involves combining the mRNA with lipid nanoparticles, then filling vials, boxing vials, and freezing them.[82] Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids.[83] As of mid-November 2020, the major bottleneck in the manufacturing process was combining mRNA with lipid nanoparticles.[82]
Advance orders and logistics
See also: COVID-19 vaccine § Supply chain
The first doses of the vaccine in December 2020 are being manufactured at a Pfizer-owned production plant in Puurs, Belgium.[84]
Pfizer indicated in its 9 November press release that 50 million doses could be available by the end of 2020, with about 1.3 billion doses provided globally by 2021.[19] In July 2020, the vaccine development program Operation Warp Speed had placed an advance order of US$2 billion with Pfizer to manufacture 100 million doses of a COVID-19 vaccine for use in the United States if the vaccine is shown to be safe and effective.[85][86][87] On 9 November, the Pfizer-BioNTech partnership announced that the company is a supplier of a COVID-19 vaccine if proven to be successful and licensed.[30]
Pfizer also has agreements to supply 300 million doses to the European Union,[88] 120 million doses to Japan,[89] 40 million doses (10 million before 2021) to the United Kingdom,[21] 20 million doses to Canada,[90] and 34.4 million doses to Mexico.[91] Fosun also has agreements to supply 10 million doses to Hong Kong and Macau.[92] The Hong Kong government said it would receive its first batch of one million doses by the first quarter of 2021.[93]
BioNTech and Fosun agreed to supply Mainland China with a batch of 100 million doses in 2021, subject to regulatory approval. The initial supply will be delivered from BioNTech's production facilities in Germany.[94]
In total, only affluent countries have preorder agreements with Pfizer in 2020, and even those countries have meager or non-existent cold chain capacity for ultracold transport and storage of a vaccine that degrades within five days when thawed, and requires two shots three weeks apart.[33] The vaccine needs to be stored and transported at ultracold temperatures between −80 and −60 °C (−112 and −76 °F).[34][21][33][95][96] The head of Indonesia's Bio Farma Honesti Basyir stated that 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 only handle temperatures between 2 and 8 °C (36 and 46 °F), far above the requirements of the vaccine.[97][98]
References
According to the British National Formulary, "very rare" applies when side effects occur in less than 1 in 10,000 instances.[25]
"Swissmedic grants authorisation for the first COVID-19 vaccine in Switzerland" (Press release). Swiss Agency for Therapeutic Products (Swissmedic). 19 December 2020. Retrieved 19 December 2020.
"Comirnaty: Pending EC decision". European Medicines Agency (EMA). 21 December 2020. Retrieved 21 December 2020.
https://www.ema.europa.eu/en/documents/product-information/comirnaty-product-information-approved-chmp-21-december-2020-pending-endorsement-european-commission_en.pdf
"Regulatory Decision Summary - Pfizer-BioNTech COVID-19 Vaccine". Health Canada. 9 December 2020. Retrieved 13 December 2020.
"Regulatory Decision Summary - Pfizer-BioNTech COVID-19 Vaccine". Health Canada. 9 December 2020. Archived from the original on 9 December 2020. Retrieved 9 December 2020.
"Regulatory approval of Pfizer / BioNTech vaccine for COVID-19". Medicines and Healthcare products Regulatory Agency (MHRA). 2 December 2020. Retrieved 2 December 2020.
"FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine" (Press release). U.S. Food and Drug Administration (FDA). 11 December 2020. Retrieved 11 December 2020. This article incorporates text from this source, which is in the public domain.
"Pfizer-BioNTech COVID-19 Vaccine- rna ingredient bnt-162b2 injection, suspension". DailyMed. Retrieved 14 December 2020.
Pfizer-BioNTech COVID-19 Vaccine Emergency Use Authorization Review Memorandum (PDF). U.S. Food and Drug Administration (FDA) (Report). 14 December 2020. Retrieved 14 December 2020. This article incorporates text from this source, which is in the public domain.
"Statement by President von der Leyen on the marketing authorisation of the BioNTech-Pfizer vaccine against COVID-19". European Commission. Retrieved 21 December 2020.
"Swissmedic autorise un premier vaccin contre le coronavirus" (in French). Le Temps. 19 December 2020. Retrieved 19 December 2020.
World Health Organization (2020). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 124 – COVID-19 (special edition)" (PDF). WHO Drug Information. 34 (3): 666. Archived (PDF) from the original on 27 November 2020. Retrieved 23 November 2020.
"UK medicines regulator gives approval for first UK COVID-19 vaccine" (Press release). Medicines and Healthcare products Regulatory Agency (MHRA). 2 December 2020. Retrieved 2 December 2020.
Boseley, Sarah; Halliday, Josh (2 December 2020). "UK approves Pfizer/BioNTech Covid vaccine for rollout next week". The Guardian. Retrieved 14 December 2020.
Walsh EE, Frenck RW, Falsey AR, et al. (October 2020). "Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates". The New England Journal of Medicine. 383 (25): 2439–2450. doi:10.1056/NEJMoa2027906. PMC 7583697. PMID 33053279. Invalid |display-authors=6 (help)
Walsh EE, Frenck R, Falsey AR, et al. (August 2020). "RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study". MedRxiv: 2020.08.17.20176651. doi:10.1101/2020.08.17.20176651. PMC 7444302. PMID 32839784. Invalid |display-authors=6 (help)
Clinical trial number NCT04368728 for "NCT04368728: Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Individuals" at ClinicalTrials.gov
Palca J (9 November 2020). "Pfizer says experimental COVID-19 vaccine is more than 90% effective". NPR. Archived from the original on 9 November 2020. Retrieved 9 November 2020.
Herper M (9 November 2020). "Covid-19 vaccine from Pfizer and BioNTech is strongly effective, early data from large trial indicate". STAT. Archived from the original on 9 November 2020. Retrieved 9 November 2020.
Edwards E (9 November 2020). "Pfizer's Covid-19 vaccine promising, but many questions remain". NBC News. Archived from the original on 22 November 2020. Retrieved 12 November 2020.
Gallagher J (9 November 2020). "Covid vaccine: First 'milestone' vaccine offers 90% protection". BBC News. Archived from the original on 26 November 2020. Retrieved 9 November 2020.
"Update on our COVID-19 vaccine development program with BNT162b2" (PDF) (Press release). Mainz, Germany: BioNTech. 2 December 2020. Retrieved 12 December 2020.
Polack FP, Thomas SJ, Kitchin N, et al. (December 2020). "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine". N Engl J Med. doi:10.1056/NEJMoa2034577. PMID 33301246.
"Questions and Answers About Pfizer-BioNTech COVID-19 Vaccine". Pfizer. Retrieved 16 December 2020.
"Adverse reactions to drugs". British National Formulary. Retrieved 19 December 2020.
"Coronavirus vaccine". National Health Service. 7 December 2020. Archived from the original on 7 December 2020. Retrieved 7 December 2020.
"Bahrain becomes second country to approve Pfizer COVID-19 vaccine". Al Jazeera. Archived from the original on 4 December 2020. Retrieved 5 December 2020.
* "Coronavirus: Saudi Arabia approves Pfizer COVID-19 vaccine for use". Al Arabiya English. 10 December 2020. Archived from the original on 11 December 2020. Retrieved 10 December 2020.
* Daina Beth Solomon; Torres, Noe (11 December 2020). "Mexico approves emergency use of Pfizer's COVID-19 vaccine". Reuters. Retrieved 12 December 2020.
* Thomas K (20 November 2020). "F.D.A. Clears Pfizer Vaccine, and Millions of Doses Will Be Shipped Right Away". The New York Times. Archived from the original on 12 December 2020. Retrieved 11 December 2020.
* "First shipments of Pfizer-BioNTech vaccine in Singapore by end-Dec; enough vaccines for all by Q3 2021". The Straits Times. 14 December 2020. Retrieved 14 December 2020.
Yasmena Al Mulla (13 December 2020). "Kuwait approves emergency use of Pfizer vaccine". Gulf News. Retrieved 14 December 2020.
Campbell D (16 December 2020). "138,000 people in UK receive Covid vaccine in first week". The Guardian.
Thomas K, Gelles D, Zimmer C (9 November 2020). "Pfizer's early data shows vaccine is more than 90% effective". The New York Times. Archived from the original on 23 November 2020. Retrieved 9 November 2020.
Burger L (15 March 2020). "BioNTech in China alliance with Fosun over coronavirus vaccine candidate". Reuters. Archived from the original on 14 November 2020. Retrieved 10 November 2020.
"Pfizer and BioNTech Celebrate Historic First Authorization in the U.S. of Vaccine to Prevent COVID-19". Pfizer Inc. and BioNTech SE.
"Deep-freeze hurdle makes Pfizer's vaccine one for the rich". Bloomberg. 10 November 2020. Archived from the original on 22 November 2020. Retrieved 12 November 2020. Vaccine goes bad five days after thawing, requires two shots; Many nations face costly ramp up of cold-chain infrastructure
"Pfizer-BioNTech COVID-19 Vaccine Vaccination Storage & Dry Ice Safety Handling". Pfizer. Retrieved 17 December 2020.
Gates B (30 April 2020). "The vaccine race explained: What you need to know about the COVID-19 vaccine". The Gates Notes. Archived from the original on 14 May 2020. Retrieved 2 May 2020.
"World Health Organization timeline – COVID-19". World Health Organization. 27 April 2020. Archived from the original on 29 April 2020. Retrieved 2 May 2020.
Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, et al. (9 April 2020). "The COVID-19 vaccine development landscape". Nature Reviews Drug Discovery. 19 (5): 305–06. doi:10.1038/d41573-020-00073-5. ISSN 1474-1776. PMID 32273591.
Fauci AS, Lane HC, Redfield RR (March 2020). "Covid-19: Navigating the uncharted". The New England Journal of Medicine. 382 (13): 1268–69. doi:10.1056/nejme2002387. PMC 7121221. PMID 32109011.
Papadopoulos C (14 December 2020). "Chronologie - So entstand der Corona-Impfstoff von Biontech" [Chronology - That's how the Covid-vaccine of Biontech was being developed] (in German). Stuttgart, Germany: Südwestrundfunk. Retrieved 20 December 2020.
《Fosun Pharma and BioNTech form COVID-19 vaccine strategic alliance in China》（Fosun Phrama News Content , 15 March 2020）
"BioNTech gets $445 million in German funding for vaccine". Bloomberg.com. 15 September 2020. Archived from the original on 9 November 2020. Retrieved 10 November 2020.
"Germany: Investment Plan for Europe – EIB to provide BioNTech with up to €100 million in debt financing for COVID-19 vaccine development and manufacturing". European Investment Bank. 11 June 2020. Archived from the original on 9 November 2020. Retrieved 10 November 2020.
"Pfizer CEO says he would've released vaccine data before election if possible". Axios. 9 November 2020. Archived from the original on 10 November 2020. Retrieved 11 November 2020.
Gaebler C, Nussenzweig MC (October 2020). "All eyes on a hurdle race for a SARS-CoV-2 vaccine". Nature. 586 (7830): 501–2. doi:10.1038/d41586-020-02926-w. PMID 33077943. S2CID 224808629.
Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. (October 2020). "Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults". Nature. 586 (7830): 589–593. doi:10.1038/s41586-020-2639-4. PMID 32785213. S2CID 221126922.
"China's Fosun to end BioNTech's COVID-19 vaccine trial, seek approval for another". Reuters. 3 November 2020. Archived from the original on 12 December 2020. Retrieved 21 November 2020.
World Health Organization. "INN: Tozinameran". WHO MedNet. Retrieved 1 December 2020.
World Health Organization. "Messenger RNA encoding the full-length SARS-CoV-2 spike glycoprotein" (DOC). WHO MedNet. Retrieved 16 December 2020.
Pallesen J, Wang N, Corbett KS, Wrapp D, Kirchdoerfer RN, Turner HL, et al. (August 2017). "Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen". Proceedings of the National Academy of Sciences of the United States of America. 114 (35): E7348–E7357. doi:10.1073/pnas.1707304114. PMC 5584442. PMID 28807998.
"Pfizer-BioNTech COVID-19 vaccine: Health Canada recommendations for people with serious allergies". Health Canada. 12 December 2020.
"Public Assessment Report Authorisation for Temporary Supply COVID-19 mRNA Vaccine BNT162b2 (BNT162b2 RNA) concentrate for solution for injection" (PDF). Regulation 174. MHRA. 15 December 2020.
Hannah B (7 October 2020). "EMA begins rolling review of BNT162b2 COVID-19 vaccine". European Pharmaceutical Review. Archived from the original on 11 November 2020. Retrieved 11 November 2020.
Tiggle N (9 December 2020). " Covid-19 vaccine: Allergy warning over new jab". BBC News. Archived from the original on 9 December 2020. Retrieved 9 December 2020.
"UK medicines regulator gives approval for first UK COVID-19 vaccine". Medicines and Healthcare products Regulatory Agency (MHRA). 2 December 2020. Archived from the original on 2 December 2020. Retrieved 2 December 2020.
Neergaard L, Kirka D (2 December 2020). "Britain OKs Pfizer vaccine and will begin shots within days". AP. Archived from the original on 6 December 2020. Retrieved 6 December 2020.
Mueller B (2 December 2020). "U.K. Approves Pfizer Coronavirus Vaccine, a First in the West". The New York Times. Retrieved 2 December 2020.
Roberts M (2 December 2020). "Covid Pfizer vaccine approved for use next week in UK". BBC News Online. Archived from the original on 2 December 2020. Retrieved 2 December 2020.
Henley J, Connolly K, Jones S (3 December 2020). "European and US experts question UK's fast-track of Covid vaccine". The Guardian. Archived from the original on 9 December 2020. Retrieved 9 December 2020.
"First patient receives Pfizer Covid-19 vaccine". 8 December 2020. Archived from the original on 8 December 2020. Retrieved 8 December 2020 – via www.bbc.co.uk.
"Bahrain becomes second country to approve Pfizer COVID-19 vaccine". Al Jazeera. Retrieved 5 December 2020.
"Pfizer-BioNTech COVID-19 Vaccine (tozinameran)". Government of Canada. 16 December 2020.
"Drug and vaccine authorizations for COVID-19: List of applications received". Health Canada. 9 December 2020. Retrieved 9 December 2020.
"Mexico Approves Pfizer Vaccine for Emergency Use as Covid Surges". Bloomberg. 12 December 2020. Retrieved 12 December 2020.
"Kuwait authorizes emergency use of Pfizer-BioNTech COVID-19 vaccine". Arab News. 13 December 2020. Retrieved 15 December 2020.
"Singapore approves use of Pfizer's COVID-19 vaccine". AP News. 14 December 2020. Retrieved 15 December 2020.
"Jordan approves Pfizer-BioNTech Covid vaccine". France 24. 15 December 2020. Retrieved 15 December 2020.
"Oman issues licence to import Pfizer BioNTech Covid vaccine - TV". Reuters. 15 December 2020. Retrieved 16 December 2020.
"Chile y Ecuador se adelantan en Sudamérica y autorizan la vacuna de Pfizer". El Pais. Retrieved 17 December 2020.
"Saudi Arabia to Launch Its Coronavirus Vaccination Program" (in Spanish). Boomberg. Retrieved 17 December 2020.
"Emergency Use Authorization for vaccines explained". U.S. Food and Drug Administration (FDA). 20 November 2020. Archived from the original on 20 November 2020. Retrieved 20 November 2020. This article incorporates text from this source, which is in the public domain.
"Pfizer-BioNTech COVID-19 Vaccine EUA Letter of Authorization" (PDF). U.S. Food and Drug Administration (FDA). 11 December 2020. This article incorporates text from this source, which is in the public domain.
"Pfizer-BioNTech COVID-19 Vaccine EUA Fact Sheet for Healthcare Providers" (PDF). Pfizer. 11 December 2020.
Sun LH, Stanley-Becker I. "CDC greenlights advisory group's decision to recommend Pfizer vaccine for use". The Washington Post. Retrieved 14 December 2020.
"The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020" (PDF). MMWR. 69. December 2020.
"COVID-19: Switzerland can start vaccinating vulnerable groups already in December" (Press release). Federal Office of Public Health. 19 December 2020. Retrieved 19 December 2020.
"EMA recommends first COVID-19 vaccine for authorisation in the EU". European Medicines Agency (EMA) (Press release). 21 December 2020. Retrieved 21 December 2020.
Mezher, Michael (21 December 2020). "EU authorizes Pfizer-BioNTech COIVD vaccine". Regulatory Affairs Professionals Society. Retrieved 21 December 2020.
Bostock N (9 December 2020). "MHRA warning after allergic reactions in NHS staff given COVID-19 vaccine". GP. Archived from the original on 9 December 2020. Retrieved 9 December 2020.
Booth, William; Cunningham, Erin (9 December 2020). "Britain warns against Pfizer vaccine for people with history of 'significant' allergic reactions". The Washington Post. Archived from the original on 9 December 2020. Retrieved 9 December 2020.
Cabanillas, Beatriz; Akdis, Cezmi; Novak, Natalija (2020). "Allergic reactions to the first COVID‐19 vaccine: A potential role of Polyethylene glycol?". Allergy. doi:10.1111/all.14711. PMID 33320974. S2CID 229284320.
FURTULA, ALEKSANDAR; JORDANS, FRANK (21 December 2020). "EU regulator gives conditional approval to Pfizer-BioNTech COVID-19 vaccine". The Globe and Mail Inc. Reuters.
Johnson, Carolyn Y. (17 November 2020). "A vial, a vaccine and hopes for slowing a pandemic — how a shot comes to be". The Washington Post. Washington, D.C.: WP Company LLC. Retrieved 21 December 2020.
Mullin, Rick (25 November 2020). "Pfizer, Moderna ready vaccine manufacturing networks". Chemical & Engineering News. Washington, D.C.: American Chemical Society. Retrieved 21 December 2020.
"First doses of Pfizer-BioNTech Covid-19 vaccine being shipped from Belgium to Britain". The Straits Times. 3 December 2020. Archived from the original on 9 December 2020. Retrieved 8 December 2020.
Erman M, Ankur B (22 July 2020). "U.S. to pay Pfizer, BioNTech $1.95 bln for millions of COVID-19 vaccine doses". Reuters. Archived from the original on 22 July 2020. Retrieved 22 July 2020.
"U.S. Government Engages Pfizer to Produce Millions of Doses of COVID-19 Vaccine". US Department of Health and Human Services. 22 July 2020. Archived from the original on 22 July 2020. Retrieved 23 July 2020.
Nazaryan A (9 November 2020). "So is Pfizer part of Operation Warp Speed or not? Yes and no". Yahoo Financial News. Archived from the original on 10 November 2020. Retrieved 9 November 2020.
Pleitgen F (11 November 2020). "EU agrees to buy 300 million doses of the Pfizer/BioNTech Covid-19 vaccine". CNN. Archived from the original on 24 November 2020. Retrieved 26 November 2020.
"Japan and Pfizer reach COVID-19 vaccine deal to treat 60 million people". The Japan Times. 1 August 2020. Archived from the original on 10 November 2020. Retrieved 21 November 2020.
Tasker JP (9 November 2020). "Trudeau says promising new Pfizer vaccine could be 'light at the end of the tunnel'". CBC News. Archived from the original on 9 November 2020. Retrieved 9 November 2020.
Salud Sd. "233. Firma secretario de Salud convenio con Pfizer para fabricación y suministro de vacuna COVID-19". gob.mx (in Spanish). Retrieved 17 December 2020.
Ng E (27 August 2020). "Fosun Pharma to supply Covid-19 vaccine to Hong Kong, Macau once approved". South China Morning Post. Archived from the original on 20 November 2020. Retrieved 21 November 2020.
Ting, Victor; Lau, Chris; Wong, Olga (11 December 2020). "Hong Kong buys 15 million Covid-19 vaccine doses from Sinovac, Pfizer". South China Morning Post. Retrieved 18 December 2020.
"BioNTech and Fosun Pharma to Supply China with mRNA-based COVID-19 Vaccine" (Press release). BioNTech. 16 December 2020. Retrieved 16 December 2020.
Kollewe J. "Pfizer and BioNTech's vaccine poses global logistics challenge". The Guardian. Archived from the original on 10 November 2020. Retrieved 10 November 2020.
Newey S (8 September 2020). "Daunting task of distribution exposed as it emerges some vaccines must be 'deep frozen' at −70C". The Telegraph. Archived from the original on 9 November 2020. Retrieved 10 November 2020.
"How China's COVID-19 could fill the gaps left by Pfizer, Moderna, AstraZeneca". Fortune. 5 December 2020. Archived from the original on 12 December 2020. Retrieved 5 December 2020.
"Pfizer's Vaccine Is Out of the Question as Indonesia Lacks Refrigerators: State Pharma Boss". Jakarta Globe. 22 November 2020. Archived from the original on 7 December 2020. Retrieved 5 December 2020.
External links
Scholia has a profile for tozinameran (Q97154240).
"Tozinameran". Drug Information Portal. U.S. National Library of Medicine.
Global Information About Pfizer‑BioNTech COVID‑19 Vaccine (also known as BNT162b2)
A phase 1/2/3, placebo-controlled, randomized, observer-blind, dose-finding study to evaluate the safety, tolerability, immunogenicity, and efficacy of SARS-COV-2 RNA vaccine candidates against COVID`-19 in healthy individuals Original study protocol (by Pfizer)
Pfizer and BioNTech Announce Vaccine Candidate Against COVID-19 Achieved Success in First Interim Analysis from Phase 3 Study（press release by Pfizer, 2020-11-09）
Information for UK Healthcare Professionals on COVID-19 mRNA Vaccine BNT162b2 concentrate for solution for injection
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COVID-19 pandemic
