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🌏 | EU, Pfizer vaccine delivery completed in September next year


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EU and Pfizer vaccines will be delivered in September next year.

 
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Currently, the only new corona vaccine approved in the EU is made by Pfizer.
 

[Brussels XNUMXth Reuters] -European Union (EU) executive body, European Commission on XNUMXth, US Pharmaceutical University ... → Continue reading

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COVID-19 vaccine

COVID-19 vaccine(Covid 19 vaccine,British: COVID-19 vaccine) IsNew coronavirus infection (COVID-19)AgainstAcquired immunity (acquired immunity) With the aim of providing several differentvaccineA general term for technology.Previous research to develop a vaccine against this coronavirus infection, ieSARSandMERSResearchCoronavirusEstablishing knowledge about the structure and function of2020Accelerated the development of various technology platforms for the COVID-19 vaccine in the early days[1].

As of February 2021, 2 vaccine candidates worldwideUnder clinical research17 is a phase I study, 23 is a phase I / II study, 6 is a phase II study, and 20 is a phase III study.[2][3][4][5]..The other four candidates have completed the exam[3]..In Phase III clinical trials, some COVID-19 vaccines are as high as 19% for the prevention of symptomatological COVID-95 infectionsEffectivenessIs shown. As of February 2021, 2 vaccines are available in at least one countryRegulatory authorityApproved for general public use. Two typesRNA vaccine(Pfizer-BioNTech Vaccine,Moderna vaccine), 4 types of conventional typeInactivated vaccine((English edition,(English edition,CoronaVac,(English edition), 4 typesViral vectorvaccine(Sputnik V,Oxford-AstraZeneca vaccine,(English edition,Johnson & Johnson Vaccine), 1 typesPeptide vaccine((English edition)[3]..In many countries, such as the elderlycomplicationsPlans are being implemented to prioritize and phase out those who are at the highest risk of infection and those who are at high risk of exposure or infection, such as healthcare workers.[6].. As of February 2021, 2, the COVID-26 vaccine has been administered 19 million times worldwide, based on official reports from health agencies in each country.[7]..Pfizer, Moderna and AstraZeneca predict that they will have 3 billion production capacities in 2021 and will be able to vaccinate about 53 billion people (protective effect against COVID-30). (Because two inoculations are required to obtain it). By December 19, more than 2 billion vaccines have been pre-ordered from each country[8], High-income countries, which make up 14% of the world's population, buy about half of them[9].

Overview

2020 eraAs the COVID-19 infection spread at a rapid pace, research institutes and drug manufacturers in each country set out to develop new vaccines and reassess existing vaccines developed for other viruses. ..who(WHO)2020Published a list of 5 plans in progress worldwide by May.Eight of them have plansWestern,ChugokuClinical trialIs in the stage of[10]..In addition, WHO is a framework for joint investment and purchase by each country in vaccine development.COVAX(Kobax)Was launched[11].

Regarding the first vaccine to be developed, it is possible to develop a type of vaccine that prevents aggravation and death rather than infection prevention.[12].. Others have pointed out that the vaccine is not effective for the elderly.[13].

Some companies are looking for new manufacturing methods for the production of vaccines for COVID-19. This is the traditionalChicken eggsbyInfluenza vaccineThis is because there is a risk that the productivity will be low and it will take time if the production method of is applied, and the virus injected into the egg may be mutated to reduce the effectiveness of the vaccine.[14].. In particular,DNA vaccine,mRNA vaccineIs under development[15].

WHO,Coalition for Epidemic Infectious Diseases Innovation (Coalition for Epidemic Preparedness Innovations, CEPI) ,andGates Foundation(GF) Is investing funding and organizational resources in anticipation of the need for several vaccines to prevent the continuation of COVID-19 infection[16]..CEPI organizes a $ 20 billion global fund for rapid investment and development of vaccine candidates[17]Showed in September 2020 that clinical data to assist in licensing may be available by the end of the year. On May 9, 2020, a teleson hosted by WHO (Long time special program), $ 40 billion pledges from 81 countries[18]..At the same time, WHO also announced the development of an international "solidarity trial" for the simultaneous evaluation of multiple vaccine candidates that have reached Phase II / III clinical trials.[19].

2020 year 11 month,バーレーンIs in ChinaShino FarmGiven the urgent marketing approval of the company vaccine,United Arab Emirates(UAE) followed. In December, with Bahrain英国Is ricePfizerApproved for emergency use of company vaccine[20][21], UAE andカナダApproved for general use[22][23][24].

History

SARS and MERS

As of 2003, avian infectious bronchitis virus (infectious bronchitis virus),Canine coronavirusVaccines have been manufactured against several animal diseases caused by the coronavirus, such as feline coronavirus.[25]..Affect humansCoronavirusBranch Ofウ イ ル スPrevious projects for developing vaccines againstSevere acute respiratory syndrome(SARS) andMiddle East respiratory syndrome(MERS) was targeted. SARS[26]And MERS[27]Vaccines against non-humanWith animalsHas been tested.

According to studies published in 2005 and 2006, the identification and development of new vaccines and medicines to treat SARS was a priority for governments and health agencies around the world at the time.[28][29][30].. As of 2020, there are no cures or preventative vaccines that have been proven safe and effective against human SARS.[31][32].

There is no established vaccine for MERS[33].. When MERS became widespread, existing SARS studies were thought to have the potential to provide useful templates for developing vaccines and treatments for MERS-CoV infection.[31][34].. As of March 2020, one (DNA-based) MERS vaccine that has completed Phase I clinical trials in humans[35], And 3 other vaccines are in progress, all of which are adenovirus vector type 2 (ChAdOx1-MERS, BVRS-GamVac) and MVA vector type 1 (MVA-MERS-S).[36].

2020 COVID-19 vaccine development

Infectious disease vaccines have never been manufactured within a few yearsHuman capitalNo vaccine exists to prevent coronavirus infection[16].. After the coronavirus was detected in December 2019[37], COVID-19Gene sequenceWas released on January 2020, 1, triggering an urgent international response to expedite the development of preventative vaccines in case of an outbreak.[38][39][40].

2020 year 2 month,who(WHO) is the causative virusSARS coronavirus 2He said he did not expect a vaccine against (SARS-CoV-2) to be available within 18 months.[41].. The global surge in COVID-2020 infection rates in early 19 stimulated international alliances and government efforts to urgently organize resources for the rapid production of multiple vaccines.[19]In March, four vaccine candidates were included in the human evaluation ("Clinical trials started in 2020Refer to the table)[38][42].

In April 2020, WHO will spend a total of 4 billion to develop three or more vaccines with different technologies and distributions.U.S. dollarEstimated[19][43].. By April 2020, "almost 4 companies and research institutes in 19 countries" will be in this virtualgold RushWas working on[44]..Also in April, CEPI selected six vaccine candidates for COVID-4 for development through Phase II-III trials by the International Union, with three final vaccines. Estimates that it must be streamlined through regulation and quality assurance to obtain a license[2][16][42]..Another analysis shows that 10 vaccine candidates require initial development at the same time, and 10 vaccine candidates require initial development at the same time before some of them are selected as the final path to licensing. I'm estimating.

July 2020, UK National Cyber ​​Security Center (National Cyber ​​Security Center), The United States and Britain of their respective governments and militaryIntelligence agencyAnd the security organization, Communications Security Establishment of Canada (Communications Security Establishment),United States Department of Homeland SecurityDirectorate General of National Protection and Programs (Cybersecurity Infrastructure Security Agency),US National Security Agency(NSA)ロシアNational supporthackerClaimed that it may have attempted to steal COVID-19 treatment and vaccine research from academic and pharmaceutical institutions in other countries.Russia denied it[45].

Developmental status

During 2020, the major changes in the overall COVID-19 vaccine development efforts from the beginning of the yearMultinational pharmaceutical industryIncreasing joint research with governments and many countries focusing on COVID-19 vaccineBiotechnologyCorporate diversity and growth[2].. According to CEPI, the general geographical distribution of COVID-19 vaccine development is:North AmericaOrganization accounts for about 19% of the world's COVID-40 vaccine researchAsiaAustralia30% in Europe, 26% in Europe,South AmericaAnd there are several projects in Africa[38].

International organization

Some organizations are forming international partnerships to accelerate vaccine development and prepare for distribution, some of which began raising US $ 2020 billion in early May 5, unprecedented in history. Promoting cooperation, accelerating research, and international communication on a scalewho(WHO) is also included[18].. WHO also has Covid-19 Vaccines Global Access to coordinate global vaccine development (COVAX)GAVIAnd in collaboration with CEPI Access to COVID-19 Tools (ACT) Accelerator Is the pillar of the vaccine[2][46][47].. In July, WHO announced that 7 countries, which make up up to 60% of the world's population, have agreed on a WHO COVAX program for the fair and equitable distribution of the final licensed vaccine. COVAX aims to accelerate the development and production of the COVID-165 vaccine and ensure that "access to licensed vaccines is provided fairly to all countries."In particular2021By the end, participating countries will protect front-line healthcare workers and high-risk people and vaccinate the most vulnerable 20% of the population[48]Guarantee that you will receive a guaranteed amount (provide up to 20 billion doses equally)[49][50].

CEPI, in collaboration with international health authorities and vaccine developers, has created an additional US $ 20 billion fund.A global partnership between public, private, philanthropic and civil society organizations that has funded research and clinical trials of eight vaccine candidates for the foreseeable future (8-2020). The goal is to support some candidates for full development[2][43]..United Kingdom, Canada,ベルギー,ノルウェー,スイス,Germany, NetherlandsHas already donated US $ 9 million[18][51], A private charity specializing in vaccine research and distributionBill & Melinda Gates Foundation(Gates Foundation) has donated US $ 2 million[52][53].

From London, England, June 2020, 6G7andG2035 of the countriesHead of StateAmong private and government representatives from 52 countries, includingVirtualThe summit was adjusted and US $ 88 billion was raised.Global Alliance for Vaccines and Vaccinations (GAVI)By2025Prepare for vaccines for 3 million children in developing countries by[54]..The main donation is US $ 16 billion from the Gates Foundation[55]And the UK government for five years, including £ 5m a year (about US $ 3 billion in June 3000).

As of December 2020, US $ 12 billion has been raised by ACT Accelerators, nine vaccine candidates have been funded by COVAX and CEPI, and 24 countries are working on final vaccine deployment plans.[56][57].

Coalition for Epidemic Control Innovation (CEPI)

Coalition for Epidemic Infectious Diseases Innovation Theノルウェーgovernment,Indiagovernment,Bill & Melinda Gates Foundation, And charitable trust organizationsWelcome TrustFunded in 2017World Economic Forum(DavosPublic institutions, private institutions, which were established at the conference)CharityAnd a global collaboration between civil society[58].Japan OfMinistry of Health, Labor and WelfareHas also been involved in the foundation and contributed since 2017[59].

On January 2020, 1, CEPI began work on vaccine development by the following three research teams, with at least one vaccine.Clinical trialAnnounced that it will start by June[59][60].. He also conducted clinical trials on humans in the summer, and said that approval of the vaccine would be as early as this year[61].

  1. US drug/vaccine developmentModerna, Inc.(English) (MRNA.O) andNational Institute of Allergy and Infectious Diseases (NIAID) cooperation
  2. Pharmaceutical companyInovio Pharmaceuticals, Inc. (INO.O)
  3. HoweQueensland UniversityTeam

In addition, the US company has joined the vaccine development plan,SARS,MERSIdentified from survivors ofMonoclonal antibodyWhether (mAbs) is effective against this virus[62].

Inovio has MERS' most advanced vaccine candidate INO-4700[63], The virus could be designed within 3 hours after the DNA sequence of the virus was published. Up to $ 900 million (about 9 million yen) from CEPISubsidyIn the early summer of 2020Middle East-AfricaLocalPhase II clinical trialGoing into[64][65]Wants to conduct large-scale clinical trials in China by the end of the year[66].

February 2, UKGlaxoSmithKline (GSK) isPandemicEstablished with a vaccineAdjuvantAnnounced to participate in the collaboration of CEPI to provide the basic technology of (antigenicity enhancer)[67].

XNUM X Month X NUM X Day,ModernaIs a safety study of administering the COVID-19 vaccine under development to humans (Phase I study) For US allergiesInstitute of Infectious Diseases (NIAID) Shipped to.Clinical trials in humans are expected to begin within two months, but may take a year and a half to become generally available.[68].

Japan

August 2020, 3,Mitsubishi Tanabe PharmaAnnounced that it will start developing vaccines using plant-derived particles manufactured by a Canadian subsidiary.[69].

August 2020, 3,Osaka UniversityDrug discovery companyAngesDeveloped a vaccine for this virus in collaboration with Osaka University,Takara BioAnnounced that it will manufacture[70][71][72].. The clinical trial will start on June 6, the same year, and will be conducted for 30 people by the end of July.[73][74].DNAPlasmidUtilizing technologyDNA vaccineIt is said that the manufacturing process can be completed in a shorter time than other methods of vaccines.

August 2020, 5,Shionogi PharmaceuticalIs a subsidiary of UMN PharmaNational Institute of Infectious DiseasesIn collaboration with, it announced that it is aiming to start clinical trials within the year. The clinical trial is scheduled to start in 2020 at the earliest. It is expected to be launched in the market in the fall of 2021, with the goal of producing 3,000 million people by the end of the same year.[75][76].

Daiichi Sankyo,Tokyo UniversityThe Institute of Medical Sciences aims to start clinical trials of vaccines from March 2021 at the earliest.[76].

August 2020, 6,Kyushu UniversityIs from Kyushu UniversityVenture company(Fukuoka City) announced that it has succeeded in developing a protein that is a candidate for a vaccine for the new coronavirus.[77][78].. Aiming to start clinical trials of vaccine from 2021[78].

In Japan, Pfizer applied for approval to the Ministry of Health, Labor and Welfare on December 2020, 12, and domestic manufacturers and universities are mainly developing five vaccines with the aim of putting them into practical use, all of which are in 18. The goal is to start clinical trials in Japan, and it has not been put into practical use yet.[79].

On February 2021, 2, AstraZeneca filed an application for approval with the Ministry of Health, Labor and Welfare.[80].

February 2021, 2, Pfizer's corona vaccine "CommunityWas approved, and was officially approved on February 2021, 2.[81][82]..The legal name of the vaccine is "Coronavirus-modified uridine RNA vaccine (SARS-CoV-2)".[83].

Securing vaccine

October 2020, 6- Katsunobu KatoThe Minister of Health, Labor and Welfare (at that time) announced that he would establish a mass production system for corona vaccines by the first half of 2021, and with the second supplementary budget of 2020 billion yen in 2, he would accelerate the development of the production system for vaccine development companies. Showed a policy to subsidize the cost to proceed[84].

October 2020, 6- Shinzo AbePrime Minister(At that time)Nico Nico Live Broadcast"We are negotiating with Moderna in the US and AstraZeneca in the UK so that we can get the vaccine at the end of the year at the earliest."[85].

United States Federal GovernmentA senior official in charge of the vaccine strategy "Operation Warp Speed" said on June 2020, 6, "The top priority is to protect the American people. It does not prevent other countries from getting the surplus."[86].

On September 2020, 9, the Japanese government announced a policy to make all citizens free of charge for coronavirus vaccination without asking for their own expenses.[87].

August 2021, 1,Yoshii KanThe Prime MinisterTaro KonoMinister for Regulatory ReformThe minister in charge of vaccination "Minister in charge of new coronavirus vaccinationAppointed to[88]..On January 1th, after approving the vaccine in mid-February, vaccination was started from the medical staff who participated in the safety survey from the end of February, and since then, the medical staff, the elderly aged 19 and over, and the elderly After giving priority to vaccinations for people working in facilities and facilities for persons with disabilities and those with a disease, it is assumed that vaccinations will be given to the general public in May and will be given to all citizens aged 2 and over by July. Schedule announced by the government[89].

As of January 2021, 1, the Japanese government has signed contracts with three companies, Moderna, AstraZeneca, and Pfizer, on the premise of successful vaccine development.[79].

From 2021,HyogoAshiyaHeadquartered inMedicineManufacturer,JCR PharmaIs planning to manufacture the undiluted solution of AstraZeneca's vaccine for Japan for 9,000 million doses (for 4,500 million people) in Japan.[90].

Prior to vaccination in each municipality in Japan20211/27,KanagawaKawasaki City OfKawasaki City College of Nursing OfgymnasiumAnd with Kawasaki CityMinistry of Health, Labor and WelfareVaccination training was conducted by[91].

Also, on October 2021, 1,TokyoNerima-kuHowever, small scale for vaccination scheduled to start after April 2021ClinicMainly vaccination in Japan, combined with large-scale vaccination in public facilitiesNerima Ward modelThe Ministry of Health, Labor and Welfare provided information to local governments nationwide as a precedent case.[92].KyotoKyoto City,TochigiSano CityLocal governments all over the country have decided to introduce this "Nerima Ward model".[93][94].

20212/12ToJapanFor domesticAmerica OfPfizerThe first group of vaccines made is the Pfizer manufacturing plantベルギーからChiba OfNarita International AirportToANAArrived by plane[95]..The second flight arrived at Narita on February 2st by ANA.The third flight arrived on March 2st[96][97][98]..A maximum of about 3 million times and about 136 people were secured by these three air transports.[98].

Vaccination

20212/17To2/14ToJapanInoculation of Pfizer vaccine officially approved in Japan has started in Japan, and the first inoculationTokyoMeguro OfNational Hospital Organization Tokyo Medical Center Of院長Made against[99]..In the future, vaccinations for medical professionals will be promoted at hospitals in each prefecture.

次いで、65歳以上の高齢者に対しては4月12日に接種開始、同26日以降本格接種の開始が予定されているが、接種を受ける医療従事者の数が当初の想定より100万人多い470万人に増えたことや接種対象となる高齢者が約3600万人に上ること、日本で広く使われる注射器では1瓶から6回分を採取できないこと、ファイザーのワクチン増産が5月以降となることなどから、スケジュールの遅延が予想されている[96][100][97].

Concerns about vaccines

While the development of vaccines is urgent as of August 2020, experts are concerned that "the effect of preventing the infection itself is difficult to prove."Also, of the Institute of Medical Science, University of TokyoKen IshiiThe professor complains, "The more you hurry (vaccine development), the more you neglect to guarantee safety."[76]..In response to this concern, Dr. Sotaro Mine, a postdoctoral fellow at the National Research Institute of the United States, who specializes in virology and immunology, said, "Based on the results of animal experiments, I think that it has (infection prevention effect)." Masu "[101]It has said.

Fever etc. at the stage of clinical trialSide effectsCan be seen in some cases[76].. As of December 2020, 12, the Pfizer / BioNTech vaccine reported anaphylaxis in 20 people (27 per million) in 6 inoculations.[102]..The Moderna vaccine was reported on January 2020, 1, with 23 million inoculations causing anaphylaxis in 400 (10 per million) and all patients subsequently recovering. Was done[103].

Chugoku

On January 2020, 1, an official from the China Center for Disease Control and Prevention (CDC) said it had begun development of the vaccine.[104].. Aug. 1,GuangzhouRussiaConsulateChina announced that the new coronavirus genome was provided from China to Russia, and China and Russia started joint vaccine development[105].

The clinical trial of the developed vaccine was approved in China on March 3 (although it is unknown whether it is the same as above), with Chen Wei as the leader.Chinese PLA Military AcademyMilitary Medical Research InstituteResearchers start clinical trials[106].. On June 3China Central TelevisionAlso reported[107].

March 3, with the Institute of Biological Engineering, Academy of Military Medical Sciences(English editionIs a new type of coronavirus vaccine developed independently (Adenovirus(Media) started the first clinical trial to 108 people[108]..The project manager is Chen Wei Major GeneralSo, using the replication defective human type 5 adenovirus as a medium, S antigen of the new virus is made[108]..Seven Chen Wei teams have already been vaccinated to prevent infection[108]..Maj. Gen. Chen has a PhD in viral vaccine research and has previously received anti-SARS virus preparations andEbolaHas been announced to have succeeded in developing a vaccine for[107].

On May 2020, 5, CanSino Biologics reported that it was the first in the world to confirm the effect on humans in a phase 25 clinical trial of a viral vector vaccine that started in March of the same year.[109][110].. Aug. 6,Central Military CommissionIs a domestic vaccine "(English editionUseChinese PLADecided to authorize only to[111].7/22Started emergency use of vaccine for medical professionals[112].

May 2020, 12, ChineseShino FarmIs a domestic vaccine "(English editionThe efficacy of the vaccine was set at 79.34%, and the vaccine was approved before China on December 12, the same year.Mohammed bin Rashid Earl McTumAnnounced lower than the 86% announced by the United Arab Emirates[113]..The following day, the 31st, China's National Pharmaceutical Products Administration approved China National's "BBIBP-CorV".[114].

In February 2021, China's National Drug AdministrationSinovac BiotechDomestic vaccine "CoronaVacConditionally approved[115].

ロシア

In mid-August 2020, the Russian government approved the domestically manufactured vaccine and announced that it plans to start vaccination for medical professionals from October.[116].. Then on August 8thVladimir PutinThe president is a domestic vaccine "Gam-COVID-VacAnnounced that it was the first in the world to approve (Sputnik V).[117].

On November 2020, 11, Russia announced the first interim results of a final third-stage clinical trial in which Sputnik V was 11% more effective in preventing the onset.[118].

The United States of America

On January 2020, 1, U.S. infectious disease drug maker Novavax Inc. said it had begun developing a vaccine to prevent the virus.[119][120].

January 2020, 1, major US pharmaceutical and daily necessitiesJohnson & Johnson (J & J) announced that it has begun development of the COVID-19 vaccine.EbolaApply the technology used to develop the vaccine. This vaccine is currentlyEur-lex.europa.eu eur-lex.europa.euRwandaHas been administered in[121].. "We have already put a lot of researchers into vaccine development and are confident that we will be able to achieve some results within a month. We already have a mass production system for the global market, so once the vaccine is complete, We can ship 1 million units within a year. "[122].

August 2020, 3,National Institutes of HealthIt is,National Institute of Allergy and Infectious DiseasesAnd the mRNA vaccine developed by the biopharmacy company ModernaClinical trialAnnounced that it reached. The clinical trial isState of WashingtonSeattleBeginning in the city[123], From multiple clinical trial participants by May 5, the same yearantibodyI was able to confirm[124]..We plan to supply 1 to 5 billion doses to the world in one year.[76].

PfizerVaccine will be available in 2020. Aim to inoculate hundreds of millions of people by 2021. If the vaccine is completed in Japan, it will be supplied to Japan for 2021 thousand doses by June 6.Japanese GovernmentIs basically agreed with[76]..Later, data from early clinical trials were released on November 2020, 11, with preventive efficacy exceeding 9%.[125]..In response to this, we will apply for approval to the US Food and Drug Administration by the end of November 2020.[125].

The vaccine is targeted for production of 1 million doses a year. Production is in the United StatesFujifilmIn cooperation with a subsidiary, in JapanTakeda PharmaceuticalWill manufacture and sell from the drug substance[76].

The United Kingdom

AstraZeneca Oxford UniversityWe have jointly developed a vaccine with and have been conducting clinical trials since April 2020. It is possible to produce 4 billion times from September to next year, and it is already planned to start supplying 9 million times (10 million times in the United States and 4 million times in the United Kingdom) from September.[126].. After that, the supply plan was increased to 20 billion times, and it was basically agreed with the Government of Japan that Japan would be supplied with 1 million times, of which 2,000 million times would be supplied by March 3,000.[76].. Regarding the clinical trial, it was confirmed that some participants were suspected of having a serious adverse reaction.9/9Was interrupted from[127]Revealed that it resumed on September 9th[128].

France

February 2020, 2 in FranceSanofiThe United StatesMinistry of Health and Welfare Announced that it aims to rapidly develop a recombinant vaccine for COVID-19 in collaboration with the Biomedical Advanced Research and Development Agency (BARDA) of (HHS).[129].

India

IndiaInoculation of two domestic vaccines started on January 2, 2021, and export preparations are in progress."Kobaksin" developed by Indian companies and government agencies, and Indian companies developing AstraZenecaLicense productionAlthough it is a "Kobi Shield", the former does not show data to prove its effectiveness at the approval stage.[130].

Type of vaccine

As of January 2021, nine different technology platforms (many candidate technologies remain undefined) are under research and development to create an effective vaccine against COVID-1.[2]..Most of the vaccine candidate platforms in clinical trials are the major COVID-19 infectionsantigenCoronavirus spike asproteinAnd its variants[2].. The platform developed in 2020Nucleic acidTechnology (Nucleoside modified messenger RNAandDNA),Non-replicating viral vector,peptide,Attenuated virus,and so on[1][16][38].

Many vaccine technologies being developed for COVID-19 use a "next generation" strategy to improve the accuracy of the COVID-19 infection mechanism, unlike vaccines already used to prevent influenza. doing[1][2]..Vaccine platforms under development include healthcare professionals, the elderly, children, pregnant women and existing May improve the flexibility and effectiveness of antigen manipulation targeting the mechanism of COVID-19 infection in sensitive population subgroups, such as those with reduced illness[2][38].

COVID-19: Vaccine Technology Platform, September 2021[3]
Molecular platform[Annotation 1]Total number of candidate vaccinesTotal number of candidate vaccines in clinical trialsNumber of approvals in at least one country
Non-replica typeVirus vector3544
Inactivated virus1954
RNA based3632
Protein subunit8041
DNA-based2320
Virus-like particles1910
Replicative viral vector2300
Virus attenuated alive400

^Technologies for dozens of candidate vaccines have not been announced or are "unknown"[3]

cost

According to one expert, an effective vaccine against COVID-19 can save trillions of dollars in global economic impact, so the cost of billions of dollars looks small compared to that.[131]..In the early stages of a pandemic, it is not known if a safe, reliable, and affordable vaccine against the virus can be produced, and exactly how much it will cost to develop the vaccine. Was[16][39][52]..Billions of dollars could be invested without success[51].

Once an effective vaccine is developed, billions of vaccines need to be produced and distributed worldwide. In April 2020, the Gates Foundation estimates that manufacturing and distribution will cost as much as US $ 4 billion.[132]..84-90% of vaccine candidates in Phase I clinical trials[38][133]Did not reach final approval during development, and 25.7% did not reach approval in Phase III clinical trials[133]..Manufacturers' investments in vaccine candidates exceed US $ 10 billion, and millions of doses can be wasted if advanced manufacturing contracts are signed.[16][51][52].

As of November 2020, companies subsidized under the US Operation Warp Speed ​​program have set an initial price of $ 11 to $ 1 per flu vaccine. doing[134].. In December 2020, a Belgian politician briefly published a confidential price agreed between vaccine producers and the EU.[135] :

ManufacturervaccinePrice per dose in the EU[136]
AstraZenecaOxford-AstraZeneca COVID-19 Vaccine€ 1.78
Johnson & JohnsonJohnson & Johnson COVID-19 Vaccinefor US$8.50
Sanofi / GSK€ 7.56
Pfizer / BiontechPfizer-BioNTech COVID-19 Vaccine€ 12.00
CureVac(English edition€ 10.00
R-PharmSputnik V COVID-19 vaccinefor US$10.00
ModernaModerna COVID-19 vaccinefor US$18.00


Clinical trials and approval status

In the Phase I study, safety and preliminary doses were tested mainly in dozens of healthy subjects, and in the Phase II study, immunogenicity and dosage were tested following the success of the Phase I study. level(BiomarkerEfficacy based on), and side effects of candidate vaccines are evaluated, usually in hundreds of people.Phase I–II trials consist of preliminary safety and immunogenicity trials, usually randomized, placebo-controlled trials to determine more accurate and effective doses.Phase III trials typically involve more subjects at multiple institutions,Control groupAt the optimal dose, includingAdverse effectsTest the effectiveness of vaccines to prevent disease while monitoring (“intervention trials” or “pivotal trials”)[137][138]..Vaccine safety, efficacy, and in Phase III trials(English editionDefinitions may vary depending on the company's trials, such as the degree of side effects, the definition of infection or dose, and whether the vaccine prevents moderate or severe COVID-19 infection.[139][140][141].

Plans for ongoing clinical trials, if accumulating data in the trial provides positive or negative early insight into the effectiveness of the treatment.(English editionMay be changed as[142][143]..Indications for ongoing Phase II-III clinical trials for candidate vaccines can shorten study duration, reduce subject numbers, expedite early termination or success decisions, avoid duplication of research efforts, and Strengthen coordination on plan changes for solidarity trials between international hubs[142][144].

List of approved or approved vaccines

Each countryRegulatory authorityOf 11 vaccinesEmergency use permissionIs giving.Six of these vaccines are at least oneWHO accredited strict regulatorApproved for emergency or general use by.

Vaccines approved by emergency license or general license
Vaccine candidate drug, developer, investorDeveloping countryTechnologyCurrent phase (number of subjects)Completed phase (number of subjects)Number of emergency use permitsNumber of approvals
Pfizer-BioNTech COVID-19 Vaccine(Comirnaty, Tozinameran)[22][145][146]
Biontech,Pfizer
USA, GermanyRNA vaccine (dispersed in lipid nanoparticles)Phase III (43,448)Phase I-II (45)3611
Sputnik V COVID-19 vaccine

(Sputnik V)
Gamaleya Research Institute of Epidemiology and Microbiology

ロシアNon-replicating viral vector vaccine (adenovirus 5 and 26 vectors)Phase III (40,000)Phase I-II (76)345
Oxford AstraZeneca COVID-19 Vaccine

(AZD1222) [lower-alpha 1][148][149][150]
OxfordDe University,AstraZeneca, CEPI

英国Non-replicating viral vector vaccine (modifiedChimpanzeeAdenovirusvector, ChAdOx1)Phase III (30,000)Phase I-II (543)314
(English edition[151]
Shino Farm: Beijing Biological Products Research Institute, Wuhan Biological Products Research Institute
ChugokuCOVID-2vaccine()Phase III (48,000)Phase I-II (320)194
CoronaVac[152][153][154]
A nephew
ChugokuInactivated SARS-CoV-2 vaccinePhase III (33,620)Phase II (600)151
Moderna COVID-19 vaccine

(mRNA-1273)[155][156]
Moderna,NIAID,BARDA, CEPI

米 国RNA vaccine (dispersed in lipid nanoparticles)Phase III (30,000)Phase I-II (720)95
Johnson & Johnson COVID-19 Vaccine

(Ad26.COV2.S)[157][158][159]
Janssen Pharma,Johnson & Johnson,BIDMC

United States, NetherlandsNon-replicating viral vector vaccine (adenovirus type 26 vector)Phase III (40,000)Phase I-II (1,045)40
(English edition
(English edition, (English edition[160][lower-alpha 2]
ChugokuNon-replicating viral vector vaccine (recombinant adenovirus type 5 vector)Phase III (40,000)Phase II (508)30
EpiVac Corona[162]
Vector Institute
ロシアPeptide vaccine[162]Phase III (40,000)Phase I-II (100)11
BBV152 (Covaxin)
(English edition,(English edition
IndiaInactivated SARS-CoV-2 vaccinePhase III (25,800)Phase I (375)10
CoviVac[163]The Chumakov Center at the Russian Academy of SciencesロシアInactivated SARS-CoV-2 vaccinePhase III (30,000)Phase I-II (300)10

Vaccine candidates in human clinical trials

  1. ^ Oxford name: ChAdOx1 nCoV-19. Manufacturing in Brazil to be carried out by.[147]
  2. ^ Manufacturing partnership with the and Canadian Center for Vaccinology,, Nova Scotia[161]

Effectiveness

The efficacy of the new vaccine is in clinical trialsEffectivenessDefined by[165]..Efficacy is a comparison of the risk of a vaccinated subject getting sick and the risk of an unvaccinated subject getting sick.[165]..Clinical trials were conducted with different populations, regions, and viral variants, so it is not easy to compare the effectiveness of different vaccines.[166].. Vaccine for COVID-19(English edition67% may be enough to delay the pandemic, but this is necessary for the vaccine to prevent infectionSterilization immunityIt is premised on giving (the action of the immune system to eliminate the virus before infection).Vaccine efficacy reflects disease prophylaxis and may be highly infectious in asymptomatic individuals, making it an inadequate indicator of SARS-CoV-2 infectivity.[167].US Food and Drug Administration(FDA) andEuropean Medicines Agency(EMA) has set a cutoff value of 19% for the efficacy required for approval of the COVID-50 vaccine.[168][169].

In the calculation of efficacy, symptomatological COVID-19 is generally positive for PCR and(English editionAlthough defined as having at least one or two symptoms in the defined list of, the exact specifications will vary from study to study.By country(English editionBecause of the different prevalence of, the study site also affects the reported efficacy.The following range is 95%Confidence intervalIs.The approved and approved vaccines have shown the following efficacy:

vaccineEfficacy for symptomatological COVID-19Effectiveness against severe COVID-19Clinical trial locationReference
Moderna vaccine89-97%No case米 国[170]
Pfizer BioNTech Vaccine90-97%UnreportedMultilateral[171]
Sputnik V vaccine86-95%94-100%ロシア[172]
Oxford-AstraZeneca Vaccine62-90%[Source required]
(English edition75-95%No case英国[173][174]
20-80%No caseSouth Africa
(English edition~ 79%[175][176]
CoronaVac~ 78%~ 100%[177][178][Unreliable medical source?]
Johnson & Johnson Vaccine55–75% (moderate cases)54-97%Multilateral[179][180]
58–82% (moderate cases)-9–100%米 国
49–81% (moderate cases)8-100%Brazil
41–79% (moderate cases)46-95%South Africa

As of January 152, 2021, BBV1 has not been announced as an indication.[181].

Oxford UniversityIn early February 2021, researchers volunteered to test 2 people to evaluate the effectiveness of the mix-and-match method, which combines two different vaccines, rather than giving the same vaccine twice. Registration has started.The ultimate goal of this study is to determine if the mix-and-match method is as effective or better than the method currently in use.In this studyPfizerCompanyBiontechInjectables developed by the company in collaboration with Oxford University,AstraZenecaThey will utilize injectables developed by the company, which are two vaccines that rely on different methods to deliver information to the subject's cells.Despite Pfizer and AstraZeneca's support for the examUgur Sahin"I'm not happy with the fact that people in need will run out of potentially beneficial doses," he said in December, disagreeing with the trial.[182].

Mutant strain

PfizerIn a preliminary study by the company, for various SARS-CoV-2 variantsThe company's mRNA vaccineHas been shown to be at most insignificant in its effectiveness[183].US CDCAccording to most experts, due to the nature of the virus, it is unlikely that mutants (both innate and vaccinated) will emerge that completely escape the immune response.[184].

T cell immunity is being studied as a potential solution to the problem of reduced vaccine efficacy against related mutant strains.This is because T cells target multiple fragments of the virus.[185]..Most of the genetic variationSpike proteinBeing above, T cells that attack other parts of the virus should be able to recognize new mutants.Viral vectorandmRNA-basedVaccines are believed to elicit the strongest T cell response[186]..This is an RNA virus like SARS-CoV-2yellow feverの た め にVaccine developedBut in the virus, which is hard to change, as opposed to what is on the surfaceantigenIt is believed that targeting is the reason why the effect is long-lasting without being affected by the majority of mutations. Companies such as Emergex, Osivax, and eTheRNA are targeting these internal antigens with the aim of developing a versatile SARS-CoV-2 vaccine.[187]..Biotechnology company Gritstone is also experimenting with a vaccine that specializes in producing T cell immunity.[188][189].

January 2021, 1 of the Moscow City DumaDarya BesedinaThe Vice-Chair urged the Minister of Health of Russia to fund research on new strains and to study the efficacy of Russian vaccines against these strains.[190].. July 2021, 2,European Medicines AgencyMade a similar complaint to the vaccine maker[191].. On February 2, Russian President Vladimir Putin deployed the genome decoding of the Russian SARS-CoV-15 strain to the government within a month, funded these studies, and released a new Russian vaccine. Instructed to check if it is valid[192].

B.1.1.7 (UK) mutant strain

New in the UK in December 2020(English editionIsB.1.1.7Was confirmed[193]..Early results suggest that both the Pfizer and modelna vaccines protect against UK mutants.[194][195].. Same for B.1.1.7 mutant strainModerna vaccineAnother study on the effectiveness of[196].

501.V2 (South Africa) mutant strain

However, these vaccines are not very effective against South African mutants, and according to Moderna, the current vaccine has only 1/6 antibodies against South African mutants compared to the original virus. It reports that it did not produce.They are from South Africa(English editionStarted testing a new vaccine to tackle (also known as B.1.351)[197].. On February 2021, 2, Pfizer announced that the 17.V501 mutant had a two-thirds reduction in neutralizing activity, but the effectiveness of the vaccine to prevent disease in this mutant remains unclear. Couldn't claim[198].

January in South AfricaAd26.COV2.SJohnson & Johnson, which tested the vaccine, reported that the protection rate against moderate to severe COVID-19 infection was 72% in the United States and 57% in South Africa.[199].

August 2021, 2,Financial TimesPaper is from South Africa(English editionIn the provisional test data of the test conducted in collaboration with Oxford University,Oxford-AstraZeneca COVID-19 Vaccine Of(English editionReported that it showed a decrease in effectiveness against[200]..The study found that in a sample size of 2,000 people, the AZD1222 vaccine provided "minimal protection" in all cases except the most severe cases of COVID-19.[201].. On February 2021, 2, the South African Health Minister canceled about one million vaccine deployment plans while reviewing the data and waiting for advice on how to proceed.[202][203].

Formulation

As of 2020, 11 of the vaccine candidates under clinical development are using adjuvants to increase immunogenicity.[2].(English editionIs a substance that is added to vaccines to enhance the immune response to antigens such as COVID-19 virus and influenza virus.[204]..Specifically, adjuvants can be used to formulate COVID-19 vaccine candidates to increase their immunogenicity and efficacy to reduce or prevent COVID-19 infection in vaccinated individuals.[204][205].. The adjuvants used in the formulation of COVID-19 vaccines may be particularly effective in techniques using inactivated COVID-19 virus and recombinant protein-based or vector-based vaccines.[205]..Known as alumAluminum saltIs the first adjuvant used in an approved vaccine and is the adjuvant of choice in about 80% of adjuvanted vaccines.[205]..Alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including the release of inflammatory cytokines[204][205].

Supply chain

To deploy COVID-2021 vaccination after 19, 100-190 billion bottles (Vial) Global transportation and tracking may be required, and this effort will easily become the biggest challenge in history.[16][206][207].. As of September 2020, Supply Chain and Logistics (logistics) Experts have expressed concern that the international and domestic networks for the distribution of licensed vaccines are not ready to respond in both quantity and urgency.The reason is mainly in 2020PandemicDue to resource deterioration during downsizing that reduces the lockdown and supply capacity of[206][208][209].. The COVAX (The COVID-19 Vaccines Global Access) partnership, global pharmaceutical companies, contract vaccine manufacturers, cross-border transportation, storage facilities, national health agencies, and many other organizations are facing global coordination. About issuesGAVI OfChief executive officer(CEO)(English editionStates as follows. "Efficient delivery of billions of vaccines worldwide involves highly complex logistical and programmatic obstacles along the supply chain."[210].

As an example of emphasizing the size of the taskInternational Air Transport AssociationTransports only a single dose to people in more than 19 countries experiencing the COVID-200 pandemic, with 1 aircraft747A type freighter (introduced a precision vaccine cold storage device) is required.[211].. "In a fast-moving pandemic, if everyone isn't safe, no one is safe," GAVI said.[47].

In contrast to multi-billion dollar investments in vaccine technology and early-stage clinical research, the vaccine's post-licensing supply chain has not received similar planning, coordination, security, or investment.[206][208][212]..The main concern isLow and middle income countriesVaccine distribution resources, especially for vaccination of children, are scarce or absent.[47][213].. In September, the COVAX partnership included 9 countries coordinating plans to optimize their COVID-172 vaccine supply chain.[214],UNICEF(UNICEF) will work with COVAX to prepare funding and supply chains for vaccination of children in 92 developing countries.[215][216].

logistics

Logistics services for vaccination ensure the necessary equipment, staff and supply of licensed vaccines across international borders.[217]..The core of logistics includes vaccine handling and monitoring, cold chain management, and distribution safety within the vaccination network.[218].. The purpose of the COVAX facility is to integrate manufacturing, transportation and overall supply chain infrastructure, centralize and equally manage logistics resources among participating countries.[47][212]..Includes logistics tools for vaccine forecasting and needs estimation, domestic vaccine management, potential waste, and inventory management[218].

Other logistics factors implemented internationally during the transportation of the COVID-19 vaccine include:[206][219][220] :

  • Individual vaccineVialThebarcodeVisibility and traceability
  • Sharing of supplier audits
  • Vaccine vial transport from manufacture to recipientEvidence preservationSharing
  • Use of vaccine temperature monitoring tools
  • Temperature stability test and guarantee
  • New packaging and delivery technology
  • Stockpiling
  • Adjustment of supplies in each country (Personal Protective Equipment (PPE),(English edition, Syringe, needle, rubber stopper, refrigerated fuel and power supply, waste disposal, etc.
  • Communication technology
  • Environmental impact of each country

According to one vaccine developer, a lack of logistics at any stage could derail the entire supply chain.[221]..If the vaccine supply chain fails, the economic and human costs of a pandemic can be prolonged over the years.[209].

Manufacturing capacity

As of August 2020, months after the establishment of safety and efficacy, many governments have more than US $ 8 billion, despite some vaccine candidates entering Phase III trials. Pre-ordered more than 50 billion vaccines at a cost[207][221][222]..2021 vaccine pre-orders from the UK Government were 1 per person[207].. In September, CEPI provided financial support for basic and clinical research on nine vaccine candidates under a funding commitment to produce two billion doses of three vaccines approved by the end of 9. ing[214].2022A total of 70-100 billion COVID-19 vaccines could be produced worldwide by now, but large pre-orders (called "vaccine nationalism") by rich countries are vaccines in poorer countries. It threatens the use[16][207][221].

Indian Serum Research InstitutePlans to produce at least one billion doses of vaccine, half of which will be used in India[207].

After joining COVAX in October, China announced that it would produce 10 million vaccines by the end of 2020 and another 6 billion vaccines in 2021, but 10 billion people are home to it. It was unclear how many vaccines would be produced for the population of[223].Shino FarmThe company states that it may have a production capacity of over 2021 billion doses in 10[224].. Sinovac will complete its second production facility by the end of 2020CoronaVacIt says it aims to increase its production capacity from the previous 3 million doses to 6 million doses.[225].

AstraZeneca(English editionThe CEO said: "The challenge is not the production of the vaccine itself,VialIs in filling.There are not enough vials in the world "[226]In preparation for the high demand for vial manufacturing, an American glass maker invested $ 7 million for a vial factory in July. [1]Although there are concerns about the availability of glass for vial production and the management of contaminants[227]Shows rising manufacturing costs and diminished potential developer interests amid demand for affordable vaccines[47][207][209].

Vaccines must be handled and transported according to international regulations, maintained under different temperature controls by vaccine technology, and used for vaccination before they deteriorate during storage.[207][221].. The size of the COVID-19 vaccine supply chain is expected to be enormous to ensure global delivery to vulnerable populations.[16][208]..Priorities for preparing facilities for such distribution include optimization of temperature-controlled facilities and equipment, infrastructure, training of vaccination staff, and rigorous monitoring.[208][210][215].RFIDThe technology is being implemented to track and certify vaccine dosages along the entire supply chain from manufacturer to vaccination.[228].

2020 year 9 month,(English editionCompanyJohnson & JohnsonWith the companytechnology transfer(English editionAgreed to support the production of vaccine candidates, including production[229].. In October 2020, a partner scheduled to manufacture the first dose in December 10Lonza GroupBut in Switzerland(English editionAnnounced to manufacture vaccine candidate moderna[230]..The newly constructed 2,000-square-meter facility will begin production at 3 million doses annually.The products manufactured here will be shipped frozen at -70 ° C to Laboratorios Farmacéuticos Rovi SA in Spain for the final stages of production.[230]..Lonza's base in Portsmouth, New Hampshire aims to begin producing US-specific vaccine ingredients as early as November.[230].

Cold chain

Vaccines (and adjuvants) are inherently unstable to temperature changes and are throughout the supply chain.Cold chainRequires control and is usually kept at a temperature of 2-8 ° C (36-46 ° F)[220][231].. The technology of the COVID-19 vaccine is diverse among several new technologies, so cold chain management presents new challenges, and some vaccines that are stable during freezing but are sensitive to heat should be frozen. Some vaccines are not, and some are stable above temperature.[231]..Freezing damage and lack of personnel training in the on-site inoculation process are major concerns.[232]..If multiple COVID-19 vaccines are approved, the cold chain of vaccines may have to address all of these temperature sensitivities between different countries, where climatic conditions and local resources for temperature maintenance change. Have sex[231].Shino FarmAnd Sinovac's vaccine is an example of an inactivated vaccine in Phase III trials that can be transported using existing cold chain systems, but CoronaVac itself does not need to be frozen.[233][234].

The modRNA vaccine technology under development is difficult to control for mass production and degradation and may require storage and transportation at very low temperatures.[209]..As an example, Moderna's RNA vaccine candidate requires cold chain management at sub-freezing temperatures, although it has a limited shelf life, and BioNTech-Pfizer's RNA candidate is in transit storage from vaccine production to inoculation. Requires storage below 70 ° C[235][236].

vaccineVialContains several doses of vaccine, but is only viable for 6 hours after being punctured for the first dose and must then be discarded for cold storage and management of the inoculation process in the field. Need to pay attention[16][237].. COVID-19 vaccines are likely to be in short supply in many places during initial deployment, so vaccination staff should avoid spoilage and disposal, which typically accounts for 30% of supply.[206][237]..Cold chains are also bikesDroneVaccine transport methods in local communities such as, the need for booster administration, the use of diluents, access to vulnerable groups such as healthcare workers, children and the elderly are also challenges.[16][215][238].

Air and land transportation

International air cargo coordination is an integral part of the time- and temperature-sensitive distribution of the COVID-19 vaccine, but as of September 2020, the air cargo network is not ready for multinational deployment.[208][211][239].. "Safe delivery of the COVID-19 vaccine will be the mission of this century for the global air cargo industry, but it will not happen without careful prior planning, and the time has come for that. I. We urge governments to take the lead in facilitating cooperation across the logistics chain, preparing facilities, security arrangements, and border procedures for challenging and complex tasks. I will be the secretary general and CEO of IATA.(English editionSaid in September 2020[239].

In 2020, airlines cut headcount due to severe decline in passenger air traffic (Layoff), Shrinked the network and kept the aircraft in long-term storage[208][239].. As the leaders in the procurement and supply of COVID-19 vaccines within the WHO COVAX facility, GAVI and UNICEF are preparing for the largest and fastest vaccine deployment to date and will cooperate with international air freight transport. , Customs and border control, and may require as many as 1 freighters to deliver a single dose of vaccine to multiple countries[215][239].

Security and corruption

Widespread demand for COVID-2,000 vaccines across the supply chain, as pharmaceuticals are the world's largest fraud market and are worth about $ 19 billion annually.Counterfeit goods,theft,Bad business law,Cyber ​​attackVulnerable to[212][240]..The lack of a harmonious regulatory framework between countries, such as poor technical capacity to identify and track counterfeit and genuine vaccines, restricted access, and ineffective capacity, is vaccinated. May threaten the lives of others and perpetuate the COVID-19 pandemic[240][241]..Tracking system technology used in packaging materials is used by manufacturers to track vaccine vials throughout the supply chain.[212], Also digital and to ensure the security of the vaccination teamBiometricsUsing the tool[228][242].. April 2020,InterpolIt is,Organized crimeInfiltrate the vaccine supply chain, steal products by physical means,Information theftWarned that it may even provide counterfeit vaccines[243].

National infrastructure development

Although WHO has an "effective vaccine management" system in place[244], This includes building priorities for preparing national and quasi-national personnel and facilities for vaccine distribution, including:

  • Training staff to handle time- and temperature-sensitive vaccines
  • Robust monitoring capabilities to optimize vaccine storage and transport
  • Temperature controlled equipment / equipment
  • traceability
  • Security

Border processes for efficient handling and customs clearance within individual countries include:[217][244] :

  • Facilitate takeoff and landing clearance
  • Of flight attendantsquarantineExemption from requirements
  • Promotion of flexible operation for efficient domestic expansion
  • Grant landing priority to maintain vaccine temperature requirements

Liability

There was a future risk to the manufacturer as no physical long-term safety could be confirmed.On the other hand, on February 2020, 2,Alex OtherThe U.S. Secretary of Health and Welfare has stated that the "Public Preparation and Emergency Preparedness Act" for medical measures against COVID-19 (Public Readiness and Emergency Preparedness Act) ”Was published.The subject was "any vaccine used to treat, diagnose, cure, prevent or alleviate infection with COVID-19, or SARS-CoV-2 or its mutant virus," and the declaration was "manufacturer in vaccine production." Claims for the negligence of the medical provider who prescribes the wrong dose or the negligence of the medical provider are excluded unless there is intentional tort. "[245]..This declaration is valid in the United States until October 2024, 10.

Incorrect information

Social MediaSo, it is said that the COVID-19 vaccine is already available when it was not available.Conspiracy theoryWas also seen.The patents cited in various SNS posts includeSARS coronavirusExisting patents on gene sequences and vaccines of other strains such as COVID-19 are referenced, but not on COVID-XNUMX.[246][247].

The United States, which was selling a vaccine called "nCoV2020 spike protein vaccine" on May 5, 21.SeattleTo North Coast Biologics, based inUS Food and Drug Administration(FDA) announces that it has sent a notice of cancellation[248].

footnote

[How to use footnotes]

注 釈

  1. ^ One or more candidate vaccines are Phase II or Phase II–III Clinical trialin.

Source

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