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BNT162b2 is a COVID-19 vaccine developed by BioNTech and Pfizer and 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, and is encapsulated in lipid nanoparticles. It was selected over the BNT162 variant BNT162b1 for Phase II and III clinical trials, and in December 2020, is under evaluation for emergency use authorisation for "widespread use" by several global medicines regulators; emergency authorisation is required as the full Phase III trials, being conducted in the United States, don't end until January 2023.

In November 2020, interim analysis of the trial examined research participants who had been diagnosed with COVID-19 and received the vaccine candidate, showing that BNT162b2 may have an efficacy of over 90% in preventing infection within seven days of a second dose. The vaccination requires two doses given three weeks apart. In preliminary analysis, the vaccine candidate had no substantial safety concerns, based on an analysis of 170 cases, and showed efficacy across adult ages. The preliminary positive results indicate eligibility for an FDA emergency use authorization that may occur during late 2020. The preliminary results have not yet been peer-reviewed by outside scientists or published in a medical journal. Further, its ability to prevent severe infection in children, pregnant women, or immune-compromised people, and its duration of immune effect are unknown.

BioNTech is the developer of the vaccine, while Pfizer provides logistics, finances and oversees the clinical trials, and is the manufacturing partner of BNT162b2 worldwide, with the exception of China where the license was purchased by Fosun. Pfizer indicated in November that 50 million doses could be available globally by the end of 2020, with about 1.3 billion doses by mid-2021. Pfizer has advanced purchase agreements of about $3 billion for providing a licensed vaccine in the United States, European Union, United Kingdom, Japan, Canada, and Peru. Distribution and storage of BNT162b2 is a global logistics challenge because the mRNA vaccine needs to be kept at −70 °C (−94 °F) until hours before the two required vaccinations.

Funding

On 17 March 2020, German company BioNTech received a $135 million investment from Fosun in exchange for 1.58 million shares in BioNTech and the future development and marketing rights of BNT162b2 in China. In September 2020, the German government granted BioNTech 375 million euros ($445 million) for its COVID-19 vaccine development program at a time when Pfizer funded its portion of development costs without government funding. BioNTech had also received 100 million euros ($119 million) in financing from the European Commission and European Investment Bank in mid-2020.

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 any bureaucracy that comes with having to give reports and agree how we are going to spend the money in parallel or together, etc." Although Pfizer did enter into an agreement with the US and Operation Warp Speed about the eventual distribution of the vaccine, as with other countries.

Vaccine platform

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. The mRNA is encapsulated in lipid nanoparticles. The mutated version of the spike protein contains two proline substitutions (designated "2P") that cause it to adopt a shape that stimulates neutralizing antibodies.

The vaccine candidate BNT162b2 was chosen as the most promising among three others with similar technology developed by BioNTech. 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. In all studies, BNT162b2 was shown to have a better safety profile than the other candidates.

Clinical research

Preliminary results from Phase I–II clinical trials on BNT162b2, published in October 2020, indicated potential for its efficacy and safety. During the same month, the European Medicines Agency began a periodic review of BNT162b2.

The study of BNT162b2 is a continuous-phase trial in Phase III as of November 2020. It is a "randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals". 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 people receiving test vaccinations in multiple countries in collaboration with Pfizer and Fosun.

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 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. Side effects include aches and fever.

Emergency use authorization

On 10 November 2020, following positive interim analysis of a Phase III clinical trial in the United States, the BioNTech-Pfizer partners applied for an emergency use authorization (EUA) for BNT162b2 with the FDA, which is scheduled to review the application by mid-December. The FDA released a document explaining that an 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." Once an EUA is issued by the FDA, BioNTech-Pfizer are expected to continue the Phase III clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) of BNT162b2 in the United States. In November 2020, Pfizer submitted an EUA application for BNT162b2 in Canada.

On 2 December 2020, the United Kingdom Medicines and Healthcare products Regulatory Agency gave the vaccine "rapid temporary regulatory approval to address significant public health issues such as a pandemic", which it is permitted to do under EU regulations. It was the first COVID-19 vaccine to be approved for national use after undergoing large scale trials, and the first ever mRNA vaccine to be authorized for use in humans. The United Kingdom became the first Western country to approve a COVID-19 vaccine for national use. The vaccine was also under evaluation during December for EUA status in several other countries.

On 4 December 2020, Bahrain became the second country to give the vaccine emergency-use authorisation after an approval by its National Health Regulatory Agency. The number of vaccines purchased and the timeline of the delivery are unknown.

Advance orders and logistics

Pfizer indicated in their November 9 press release that 50 million doses could be available by the end of 2020, with about 1.3 billion doses provided globally by mid-2021. In July 2020, the vaccine development program Operation Warp Speed had placed an advance order of $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. 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.

Pfizer also has agreements to supply 300 million doses to the European Union, 120 million doses to Japan, 40 million doses (10 million before 2021) to the United Kingdom, and 20 million doses to Canada. Fosun also has agreements to supply 10 million doses to Hong Kong and Macau.

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. The vaccine needs to be stored and transported at ultracold temperatures below −70 °C (−94 °F). 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, far above the requirements of the vaccine.

See also

• mRNA-1273, from Moderna
• Timeline of human vaccines

References

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External links

• BioNTech website, with information about the company's COVID-19 vaccine development process
• 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

• Clinical trials
• COVID-19 vaccines
• Pfizer
• Nucleic acid vaccines
• Products introduced in 2020