Jump to content

History of COVID-19 vaccine development

From Wikipedia, the free encyclopedia

This is the current revision of this page, as edited by Citation bot (talk | contribs) at 22:07, 17 July 2024 (Added date. | Use this bot. Report bugs. | Suggested by Whoop whoop pull up | Category:COVID-19 vaccines | #UCB_Category 1/15). The present address (URL) is a permanent link to this version.

(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)

COVID‑19 vaccine research samples in a NIAID lab freezer (30 January 2020)
Part of a series on the
COVID-19 pandemic
Scientifically accurate atomic model of the external structure of SARS-CoV-2. Each "ball" is an atom.
Scientifically accurate atomic model of the external structure of SARS-CoV-2. Each "ball" is an atom.
Timeline
2019
2020
2021
2022
2023
Locations
By country and territory
By conveyance
International response
National responses
Medical response
Vaccines
Current vaccines
Variants
Variants of concern
Other variants
Economic impact and recession
By country
By sport
Impacts
Long COVID
Society
Politics
virus icon COVID-19 portal

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19, was isolated in late 2019.[1] Its genetic sequence was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten the development of a preventive COVID-19 vaccine.[2][3][4] Since 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[5] By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID‑19 infection.[3][6][7][8] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development shows North American entities to have about 40% of the activity, compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[2][5]

In February 2020, the World Health Organization (WHO) said it did not expect a vaccine against SARS‑CoV‑2 to become available in less than 18 months.[9] Virologist Paul Offit commented that, in hindsight, the development of a safe and effective vaccine within 11 months was a remarkable feat.[10] The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[11] with four vaccine candidates entering human evaluation in March (see COVID-19 vaccine § Trial and authorization status).[2][12]

On 24 June 2020, China approved the CanSino vaccine for limited use in the military and two inactivated virus vaccines for emergency use in high-risk occupations.[13] On 11 August 2020, Russia announced the approval of its Sputnik V vaccine for emergency use, though one month later only small amounts of the vaccine had been distributed for use outside of the phase 3 trial.[14]

The Pfizer–BioNTech partnership submitted an Emergency Use Authorization (EUA) request to the U.S. Food and Drug Administration (FDA) for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[15][16] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[17][18] becoming the first country to approve the vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine.[19][20][21] As of 21 December 2020, many countries and the European Union[22] had authorized or approved the Pfizer–BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency marketing authorization for the Sinopharm BIBP vaccine.[23][24] On 11 December 2020, the FDA granted an EUA for the Pfizer–BioNTech COVID‑19 vaccine.[25] A week later, they granted an EUA for mRNA-1273 (active ingredient elasomeran), the Moderna vaccine.[26][27][28][29]

On 31 March 2021, the Russian government announced that they had registered the first COVID‑19 vaccine for animals.[30] Named Carnivac-Cov, it is an inactivated vaccine for carnivorous animals, including pets, aimed at preventing mutations that occur during the interspecies transmission of SARS-CoV-2.[31]

In October 2022, China began administering an oral vaccine developed by CanSino Biologics using its adenovirus model.[32]

Despite the availability of mRNA and viral vector vaccines, worldwide vaccine equity has not been achieved. The ongoing development and use of whole inactivated virus (WIV) and protein-based vaccines has been recommended, especially for use in developing countries, to dampen further waves of the pandemic.[33][34]

Planning and investment

[edit]

Since 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.[5] According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development puts North American entities having about 40% of the activity compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.[5][2]

Commitment to first-in-human testing of a vaccine candidate represents a substantial capital cost for vaccine developers, estimated to be from US$14 million to US$25 million for a typical Phase I trial program, but possibly as much as US$70 million.[35][36] For comparison, during the Ebola virus epidemic of 2013–16, there were 37 vaccine candidates in urgent development with only one becoming a licensed vaccine at a total cost to confirm efficacy in Phase II–III trials of about US$1 billion.[35]

International organizations

[edit]

Access to COVID‑19 Tools (ACT) Accelerator

[edit]
Main article: Access to COVID-19 Tools Accelerator
The Access to COVID-19 Tools Accelerator (ACT Accelerator or ACT-A), or the Global Collaboration to Accelerate the Development, Production and Equitable Access to New COVID-19 diagnostics, therapeutics and vaccines, is a G20 initiative announced by pro-tem Chair Mohammed al-Jadaan on 24 April 2020.[37] A call to action was published simultaneously by the World Health Organization (WHO) on 24 April.[38] As of January 2022, it was the largest international effort to achieve equitable access to COVID-19 health technologies.[39]

National governments

[edit]

Canada announced CA$275 million in funding for 96 vaccine research projects at Canadian companies and universities, with plans to establish a "vaccine bank" that could be used if another coronavirus outbreak occurs.[40][41] A further investment of CA$1.1 billion was added to support clinical trials and develop manufacturing and supply chains for vaccines.[42] On 4 May, the Canadian government committed CA$850 million to the WHO's live streaming effort to raise US$8 billion for COVID‑19 vaccines and preparedness.[43]

China provided low-rate loans to a vaccine developer through its central bank and "quickly made land available for the company" to build production plants.[44] As of June 2020, six of the eleven COVID‑19 vaccine candidates in early-stage human testing were developed by Chinese organizations.[45] Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing the most promising vaccine candidates, prioritizing rapid evidence of efficacy over safety.[46] On 18 May, China had pledged US$2 billion to support overall efforts by the WHO for programs against COVID‑19.[47] On 22 July, China announced plans to provide a US$1 billion loan to make its vaccine accessible for Latin America and the Caribbean.[48] On 24 August, Chinese Premier Li Keqiang announced it would provide Cambodia, Laos, Myanmar, Thailand, and Vietnam priority access to the vaccine once it was distributed.[49]

US Government Accountability Office diagram comparing a traditional vaccine development timeline to a safe, possible expedited method timeline.

Great Britain formed a COVID‑19 vaccine task force in April 2020, to stimulate local efforts for accelerated development of a vaccine through collaborations of industry, universities, and government agencies. It encompassed every phase of development from research to manufacturing.[50] The vaccine development initiatives at the University of Oxford and Imperial College of London were financed with £44 million.[51][52]

In the United States, the Biomedical Advanced Research and Development Authority (BARDA), a federal agency funding disease-fighting technology, announced investments of nearly US$1 billion to support American COVID‑19 vaccine development and manufacture of the most promising candidates. On 16 April, BARDA made a US$483 million investment in vaccine developer Moderna and its partner, Johnson & Johnson.[44][53] BARDA has earmarked an additional US$4 billion for development. It will have a role in other programs for development of six to eight vaccine candidates destined for clinical study into 2021 by companies such as Sanofi Pasteur and Regeneron.[53][54] On 15 May, the government announced funding for a fast-track program called Operation Warp Speed to place multiple vaccine candidates into clinical trials by the fall of 2020 and manufacture 300 million doses of a licensed vaccine by January 2021. The project's chief advisor is Moncef Slaoui and its chief operating officer is General Gustave Perna.[55][56] In June, the Warp Speed team said it would work with seven companies developing vaccine candidates: Moderna, Johnson & Johnson, Merck, Pfizer, the University of Oxford in collaboration with AstraZeneca, and two others,[57] although Pfizer later stated that "all the investment for R&D was made by Pfizer at risk."[58]

Pharmaceutical companies

[edit]

Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), formed alliances with biotechnology companies, governments, and universities to accelerate progression to an effective vaccine.[44][45] To combine financial and manufacturing capabilities for a pandemic with adjuvanted vaccine technology, GSK joined with Sanofi in an uncommon partnership of multinational companies to support accelerated vaccine development.[59]

By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID‑19 infection.[3][6][7][8] The corporate investment and need to generate value for public shareholders raised concerns about a "market-based approach" in vaccine development, costly pricing of eventual licensed vaccines, preferred access for distribution first to affluent countries, and sparse or no distribution to where the pandemic is most aggressive, as predicted for densely-populated, impoverished countries unable to afford vaccinations.[3][45][7] The collaboration of the University of Oxford with AstraZeneca (a global pharmaceutical company based in the UK) raised concerns about price and sharing of eventual profits from international vaccine sales, arising from whether the British government and university as public partners had commercialization rights.[8] AstraZeneca stated that initial pricing of its vaccine would not include a profit margin for the company while the pandemic was still expanding.[8]

In June, AstraZeneca made a US$750 million deal allowing CEPI and Gavi, the Vaccine Alliance to manufacture and distribute 300 million doses if its Oxford vaccine candidate proved to be safe and effective, reportedly increasing the company's total production capacity to over 2 billion doses per year.[60] Commercialization of pandemic vaccines is a high-risk business venture, potentially losing billions of dollars in development and pre-market manufacturing costs if the candidate vaccines fail to be safe and effective.[3][44][45][6] Pfizer indicated it was not interested in a government partnership, considering it to be a "third party" slowing progress.[61] Further, there are concerns that rapid-development programs – like Operation Warp Speed – are choosing candidates mainly for their manufacturing advantages rather than optimal safety and efficacy.[61]

Development

[edit]

CEPI classifies development stages for vaccines as "exploratory" (planning and designing a candidate, having no evaluation in vivo), "preclinical" (in vivo evaluation with preparation for manufacturing a compound to test in humans), or initiation of Phase I safety studies in healthy people.[5] Some 321 total vaccine candidates were in development as either confirmed projects in clinical trials or in early-stage "exploratory" or "preclinical" development, as of September.[5]

Early development

[edit]
NIAID (NIH) scientist researching COVID‑19 vaccine examines agar plate. (30 January 2020)

After a coronavirus was isolated in December 2019,[1] its genetic sequence was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive vaccine.[2][3][4]

In February 2020, the WHO said it did not expect a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus, to become available in less than 18 months.[9] The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated international alliances and government efforts to urgently organize resources to make multiple vaccines on shortened timelines,[11] with four vaccine candidates entering human evaluation in March (see the table of clinical trials started in 2020, below).[2][12]

By April 2020, "almost 80 companies and institutes in 19 countries" were working on this virtual gold rush.[62] Also in April, CEPI estimated that as many as six of the vaccine candidates against COVID‑19 should be chosen by international coalitions for development through Phase II–III trials, and three should be streamlined through regulatory and quality assurance for eventual licensing at a total cost of at least US$2 billion.[5][12][63] Another analysis estimates ten candidates will need simultaneous initial development, before a select few are chosen for the final path to licensing.[63]

Cyber-espionage efforts

[edit]

In July 2020, the UK's National Cyber Security Centre, the Canadian Communications Security Establishment, and the U.S.'s Homeland Security Department Cybersecurity and Infrastructure Security Agency, and the National Security Agency (NSA) issued a joint statement saying that Russian state-backed hackers, specifically Cozy Bear (APT29) were attempting to steal COVID‑19 treatment and vaccine research from academic and pharmaceutical institutions in other countries. Russia denied the claim, but has a history of cyber-espionage and cyberattacks on foreign targets.[64][65] In November 2020, Microsoft reported that the Russian state-sponsored hacking group Fancy Bear (APT28) and North Korean state-sponsored hacking groups nicknamed "Zinc" and "Cerium" had been implicated in recent cyberattacks against researchers developing a COVID-19 vaccine (including in Canada, France, India, South Korea, and the U.S.) as well as against the World Health Organization, and that the cyberattackers had used both brute force and phishing techniques to compromise computer systems.[65] Microsoft reported that at least nine healthcare institutions were targeted, and that some attempts were successful.[66] In February 2021, South Korean's National Intelligence Service gave a closed-door briefing to members of the South Korean parliament about North Korean efforts to steal COVID-19 vaccine technology from Pfizer.[66]

Preclinical research

[edit]
NIAID (NIH) scientist researching COVID‑19 vaccine. (30 January 2020)

In April 2020, the WHO issued a statement representing dozens of vaccine scientists around the world, pledging collaboration to speed development of a vaccine against COVID‑19.[67] The WHO coalition is encouraging international cooperation between organizations developing vaccine candidates, national regulatory and policy agencies, financial contributors, public health associations, and governments, for eventual manufacturing of a successful vaccine in quantities sufficient to supply all affected regions, particularly low-resource countries.[2]

Industry analysis of past vaccine development shows failure rates of 84–90%.[2][68] Because COVID‑19 is a novel virus target with properties still being discovered and requiring innovative vaccine technologies and development strategies, the risks associated with developing a successful vaccine across all steps of preclinical and clinical research are high.[2]

To assess the potential for vaccine efficacy, unprecedented computer simulations and new COVID‑19-specific animal models are being developed multinationally.[69] Of the confirmed active vaccine candidates, about 70% are being developed by private companies, with the remaining projects under development by academic, government coalitions, and health organizations.[5] Historically, the probability of success for an infectious disease vaccine candidate to pass preclinical barriers and reach Phase I of human testing is 41–57%.[35]

Challenges

[edit]

The rapid development and urgency of producing a vaccine for the COVID‑19 pandemic may increase the risks and failure rate of delivering a safe, effective vaccine.[70][2][71] One study found that between 2006 and 2015, the success rate of obtaining approval from Phase I to successful Phase III trials was 16.2% for vaccines,[68] and CEPI indicates a potential success rate of only 10% for vaccine candidates in 2020 development.[2]

Research at universities is obstructed by physical distancing and closing of laboratories.[72][73]

Biosafety

[edit]

Early research to assess vaccine efficacy using COVID‑19-specific animal models, such as ACE2-transgenic mice, other laboratory animals, and non-human primates, indicates a need for biosafety-level 3 containment measures for handling live viruses, and international coordination to ensure standardized safety procedures.[70][2]

Antibody-dependent enhancement

[edit]
Main article: Antibody-dependent enhancement

Although the quality and quantity of antibody production by a potential vaccine is intended to neutralize the COVID‑19 infection, a vaccine may have an unintended opposite effect by causing antibody-dependent disease enhancement (ADE), which increases the virus attachment to its target cells and might trigger a cytokine storm if a vaccinated person is later attacked by the virus.[70][74] The vaccine technology platform (for example, viral vector vaccine, spike (S) protein vaccine or protein subunit vaccine), vaccine dose, timing of repeat vaccinations for the possible recurrence of COVID‑19 infection, and elderly age are factors determining the risk and extent of ADE.[70][74] The antibody response to a vaccine is a variable of vaccine technologies in development, including whether the vaccine has precision in its mechanism,[70] and choice of the route for how it is given (intramuscular, intradermal, oral, or nasal).[74]

Prior to the pandemic, ADE was observed in animal studies of laboratory rodents with vaccines for SARS-CoV, the virus that causes severe acute respiratory syndrome (SARS). Researchers therefore emphasized the need to carefully assess the potential for ADE to occur with COVID-19.[75][76] However, as of 27 January 2022 there have been no observed incidences with vaccines for COVID-19 in trials with nonhuman primates, in clinical trials with humans, or following the widespread use of approved vaccines.[33][77][76]

Trials

[edit]
Volunteer receives CoronaVac injection during Phase III trial by Sinovac in Indonesia.

In April 2020, the WHO published an "R&D Blueprint (for the) novel Coronavirus" (Blueprint). The Blueprint documented a "large, international, multi-site, individually randomized controlled clinical trial" to allow "the concurrent evaluation of the benefits and risks of each promising candidate vaccine within 3–6 months of it being made available for the trial." The Blueprint listed a Global Target Product Profile (TPP) for COVID‑19, identifying favorable attributes of safe and effective vaccines under two broad categories: "vaccines for the long-term protection of people at higher risk of COVID‑19, such as healthcare workers", and other vaccines to provide rapid-response immunity for new outbreaks.[11] The international TPP team was formed to 1) assess the development of the most promising candidate vaccines; 2) map candidate vaccines and their clinical trial worldwide, publishing a frequently-updated "landscape" of vaccines in development;[78] 3) rapidly evaluate and screen for the most promising candidate vaccines simultaneously before they are tested in humans; and 4) design and coordinate a multiple-site, international randomized controlled trial – the "Solidarity trial" for vaccines[11][79] – to enable simultaneous evaluation of the benefits and risks of different vaccine candidates under clinical trials in countries where there are high rates of COVID‑19 disease, ensuring fast interpretation and sharing of results around the world.[11] The WHO vaccine coalition will prioritize which vaccines should go into Phase II and III clinical trials, and determine harmonized Phase III protocols for all vaccines achieving the pivotal trial stage.[11]

Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials – following success in Phase I – evaluate immunogenicity, dose levels (efficacy based on biomarkers) and adverse effects of the candidate vaccine, typically in hundreds of people.[80][81] A Phase I–II trial consists of preliminary safety and immunogenicity testing, is typically randomized, placebo-controlled, while determining more precise, effective doses.[81] Phase III trials typically involve more participants at multiple sites, include a control group, and test effectiveness of the vaccine to prevent the disease (an "interventional" or pivotal trial), while monitoring for adverse effects at the optimal dose.[80][81] Definition of vaccine safety, efficacy, and clinical endpoints in a Phase III trial may vary between the trials of different companies, such as defining the degree of side effects, infection or amount of transmission, and whether the vaccine prevents moderate or severe COVID‑19 infection.[82][83][84] Phase III trials of AstraZeneca's intervention started 28 August 2020 and ended 5 March 2021.[85]

In January 2022 'Moderna' and 'Pfizer' both started trials of vaccine tailored to immunize against the Omicron variant.[86] See Response by vaccine producers for vaccine development aimed at providing immunity to Omicron.

Enrollment of participants

[edit]

Vaccine developers have to invest resources internationally to find enough participants for Phase II–III clinical trials when the virus has proved to be a "moving target" of changing transmission rate across and within countries, forcing companies to compete for trial participants.[82] As an example in June, the Chinese vaccine developer Sinovac formed alliances in Malaysia, Canada, the UK, and Brazil among its plans to recruit trial participants and manufacture enough vaccine doses for a possible Phase III study in Brazil where COVID‑19 transmission was accelerating during June.[82] As the COVID‑19 pandemic within China became more isolated and controlled, Chinese vaccine developers sought international relationships to conduct advanced human studies in several countries, creating competition for trial participants with other manufacturers and the international Solidarity trial organized by the WHO.[82] In addition to competition over recruiting participants, clinical trial organizers may encounter people unwilling to be vaccinated due to vaccine hesitancy[87] or disbelieving the science of the vaccine technology and its ability to prevent infection.[88]

Having an insufficient number of skilled team members to administer vaccinations may hinder clinical trials that must overcome risks for trial failure, such as recruiting participants in rural or low-density geographic regions, and variations of age, race, ethnicity, or underlying medical conditions.[82][89]

Eligibility criteria for AstraZeneca's Phase III trial included: Ages, 18 to 130 Years, All Sexes, and Healthy Volunteers. Inclusion Criteria specified, Increased risk of SARS-CoV-2 infection and medically stable. Exclusion criteria included; 1) confirmed or suspected immunosuppressive or immunodeficient state, 2) significant disease, disorder, or finding, and 3) Prior or concomitant vaccine therapy for COVID‑19.[85]

Adaptive design for the Solidarity trial

[edit]

A clinical trial design in progress may be modified as an "adaptive design" if accumulating data in the trial provide early insights about positive or negative efficacy of the treatment.[90][91] The WHO Solidarity trial of multiple vaccines in clinical studies during 2020, will apply adaptive design to rapidly alter trial parameters across all study sites as results emerge.[79] Candidate vaccines may be added to the Solidarity trial as they become available if priority criteria are met, while vaccine candidates showing poor evidence of safety or efficacy compared to placebo or other vaccines will be dropped from the international trial.[79]

Adaptive designs within ongoing Phase II–III clinical trials on candidate vaccines may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, avoiding duplication of research efforts, and enhancing coordination of design changes for the Solidarity trial across its international locations.[79][90]

Proposed challenge studies

[edit]
Main article: Human challenge study

Challenge studies are a type of clinical trial involving the intentional exposure of the test subject to the condition tested, an approach that can significantly accelerate vaccine development.[92][93][94][95] Human challenge studies may be ethically controversial because they involve exposing test subjects to dangers beyond those posed by potential side effects of the substance being tested.[93][94] Challenge studies have been used for diseases less deadly than COVID‑19 infection, such as common influenza, typhoid fever, cholera, and malaria.[94][95] The World Health Organization developed a guidance document with criteria for conducting COVID‑19 challenge studies in healthy people, including scientific and ethical evaluation, public consultation and coordination, selection and informed consent of the participants, and monitoring by independent experts.[96] Beginning in January 2021, dozens of young adult volunteers will be deliberately infected with COVID‑19 in a challenge trial conducted in a London hospital under management by the British government COVID‑19 Vaccine Taskforce.[97] Once an infection dose of COVID‑19 is identified, two or more of the candidate COVID‑19 vaccines will be tested for effectiveness in preventing infection.[97][needs update]

Authorizations and licensure

[edit]

At the beginning of the COVID‑19 pandemic in 2020, the WHO issued a guideline as an Emergency Use Listing of new vaccines, a process derived from the 2013–16 Ebola epidemic.[98] It required that a vaccine candidate developed for a life-threatening emergency be manufactured using GMP and that it complete development according to WHO prequalification procedures.[98]

Even as new vaccines are developed during the COVID‑19 pandemic, licensure of COVID‑19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality. In the UK and the EU, companies may use a "rolling review process", supplying data as they become available during Phase III trials, rather than developing the full documentation over months or years at the end of clinical research, as is typical. This rolling process allows the UK's regulator (MHRA) and the European Committee for Medicinal Products for Human Use to evaluate clinical data in real time, enabling a promising vaccine candidate to be approved on a rapid timeline by both the UK's MHRA and the European Medicines Agency (EMA).[99] A rolling review process for the Moderna vaccine candidate was initiated in October by Health Canada and the EMA,[100] and in November in Canada for the Pfizer-BioNTech candidate.[101]

Early authorizations in China and Russia

[edit]

On 24 June 2020, China approved the CanSino vaccine for limited use in the military and two inactivated virus vaccines for emergency use in high-risk occupations.[13] On 11 August 2020, Russia announced the approval of its Sputnik V vaccine for emergency use, though one month later only small amounts of the vaccine had been distributed for use outside of the phase 3 trial.[14] In September, the United Arab Emirates approved emergency use of the Sinopharm BIBP vaccine for healthcare workers,[102] followed by similar emergency use approval from Bahrain in November.[103]

First authorizations of RNA vaccines

[edit]

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."[104] Once an EUA is issued by the FDA, the vaccine developer is expected to continue the Phase III clinical trial to finalize safety and efficacy data, leading to application for licensure (approval) in the United States.[104] In mid-2020, concerns that the FDA might grant a vaccine EUA before full evidence from a Phase III clinical trial was available raised broad concerns about the potential for lowered standards in the face of political pressure.[105][106][107] On 8 September 2020, nine leading pharmaceutical companies involved in COVID‑19 vaccine research signed a letter, pledging that they would submit their vaccines for emergency use authorization only after Phase III trials had demonstrated safety and efficacy.[108]

Pfizer-BioNTech COVID-19 vaccine.

The Pfizer-BioNTech partnership submitted an EUA request to the FDA for the mRNA vaccine BNT162b2 (active ingredient tozinameran) on 20 November 2020.[15][16] On 2 December 2020, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine,[17][18] becoming the first country to approve this vaccine and the first country in the Western world to approve the use of any COVID‑19 vaccine.[19][20][21] On 8 December 2020, 90-year-old Margaret Keenan received the vaccine at University Hospital Coventry, becoming the first person known to be vaccinated outside of a trial,[109] as the UK's vaccination programme began.[110] However, other vaccines had been given earlier in Russia.[111] On 11 December 2020, the US Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for the Pfizer-BioNTech vaccine.[25][112] On 19 December 2020, the Swiss Agency for Therapeutic Products (Swissmedic) approved the Pfizer-BioNTech vaccine for regular use, two months after receiving the application. This was the first authorization by a stringent regulatory authority under a standard procedure for any COVID‑19 vaccine.[113][114] On 23 December, a 90-year-old Lucerne resident became the first person to receive the vaccine in continental Europe.[115]

As of December 2020, many countries and the European Union[22] have authorized or approved the Pfizer-BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency marketing authorization for the Sinopharm BIBP vaccine.[23][24] In the United Kingdom, 138,000 people had received the Pfizer-BioNTech COVID‑19 vaccine Comirnaty by 16 December, during the first week of the UK vaccination programme.[116] On 18 December 2020, the US FDA granted an EUA for mRNA-1273, the Moderna vaccine.[26][27][28] Vaccine manufacturers are awaiting full approvals to name their vaccines.[117][118]

Moderna submitted a request for an EUA for mRNA-1273 to the FDA on 30 November 2020.[119][120] On 18 December 2020, the FDA granted an EUA for the Moderna vaccine.[26][27][28]

United Kingdom

[edit]

The UK Medicines and Healthcare products Regulatory Agency (MHRA) gave the first approval to the Oxford/AstraZeneca vaccine on 30 December 2020, as its second vaccine to enter the national rollout under a conditional and temporary authorization to supply.[121][122][123]

Australia

[edit]

In October 2020, the Australian Therapeutic Goods Administration (TGA) granted provisional determinations to AstraZeneca Pty Ltd in relation to its COVID‑19 vaccine, ChAdOx1-S [recombinant] and to Pfizer Australia Pty Ltd in relation to its COVID‑19 vaccine, BNT162b2 [mRNA].[124][125] Janssen Cilag Pty Ltd was granted a provisional determination in relation to its COVID‑19 vaccine, Ad26.COV2.S, in November 2020.[126]

On 24 January 2021, the TGA granted provisional approval to Pfizer Australia Pty Ltd for Comirnaty.[127][128][129][130]

On 24 June 2021, the TGA granted provisional determination to Moderna Australia Pty Ltd for Elasomeran.[131]

European Union

[edit]

In October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) started 'rolling reviews' of the vaccines known as COVID‑19 Vaccine AstraZeneca (ChAdOx1-SARS-CoV-2) and Pfizer-BioNTech COVID‑19 Vaccine (BNT162b2).[132][133][134] The EMA released an update on the status of its rolling review of the COVID‑19 Vaccine AstraZeneca in December 2020, after the UK granted a temporary authorization of supply for the vaccine.[135]

In November 2020, the EMA published a safety monitoring plan and guidance on risk management planning (RMP) for COVID‑19 vaccines.[136] The plan outlines how relevant new information emerging after the authorization and uptake of COVID‑19 vaccines in the pandemic situation will be collected and promptly reviewed.[136] All RMPs for COVID‑19 vaccines will be published on the EMA's website.[136] The EMA published guidance for developers of potential COVID‑19 vaccines on the clinical evidence to include in marketing authorization applications.[137]

In November 2020, the CHMP started a rolling review of the Moderna vaccine for COVID‑19 known as mRNA-1273.[138]

In December 2020, the EMA received application for conditional marketing authorizations (CMA) for the mRNA vaccines BNT162b2 and mRNA1273 (Moderna Covid‑19 vaccine).[139][140] The assessments of the vaccines are scheduled to proceed under accelerated timelines with the possibility of opinions issued within weeks.[139][140][141][142]

In December 2020, the CHMP started a rolling review of the Ad26.COV2.S COVID‑19 vaccine from Janssen-Cilag International N.V.[143]

On 21 December 2020, the CHMP recommended granting a conditional marketing authorization for the Pfizer-BioNTech COVID‑19 vaccine, Comirnaty (active ingredient tozinameran), developed by BioNTech and Pfizer.[144][145][22] The recommendation was accepted by the European Commission the same day.[144][146][147][148]

On 6 January 2021, the CHMP recommended granting a conditional marketing authorization for COVID-19 Vaccine Moderna[149][150] and the recommendation was accepted by the European Commission the same day.[148][151][152]

In January 2021, the EMA received an application for conditional marketing authorization (CMA) for the COVID‑19 vaccine known as COVID‑19 Vaccine AstraZeneca, developed by AstraZeneca and Oxford University.[153] On 29 January 2021, the CHMP recommended granting the conditional marketing authorization[154][155] and the recommendation was accepted by the European Commission the same day.[156][157]

In February 2021, the CHMP started a rolling review of NVX-CoV2373, a COVID‑19 vaccine being developed by Novavax CZ AS (a subsidiary of Novavax, Inc.)[158] and a rolling review of CVnCoV, a COVID‑19 vaccine being developed by CureVac AG.[159]

In February 2021, the EMA announced that they are developing vaccine guidance to address the virus variants.[160]

In February 2021, the EMA received an application for conditional marketing authorization (CMA) for the COVID-19 Vaccine Janssen developed by Janssen-Cilag International N.V.[161] The EMA recommended a conditional marketing authorization of the COVID-19 Vaccine Janssen on 11 March 2021,[162][163] and it was accepted by the European Commission the same day.[164]

In March 2021, the CHMP started a rolling review of Sputnik V (Gam-COVID-Vac).[165] The EU applicant is R-Pharm Germany GmbH.[165]

In May 2021, the CMMP started evaluating the use of Comirnaty to include young people aged 12 to 15,[166] and it started a rolling review of Sinovac COVID-19 Vaccine.[167] The EU applicant for Sinovac is Life'On S.r.l.[167]

References

[edit]
  1. ^ a b "World Health Organization timeline – COVID-19". World Health Organization (WHO). 27 April 2020. Archived from the original on 29 April 2020. Retrieved 2 May 2020.
  2. ^ a b c d e f g h i j k l Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, Mayhew S (May 2020). "The COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (5): 305–306. doi:10.1038/d41573-020-00073-5. PMID 32273591.
  3. ^ a b c d e f Gates B (February 2020). "Responding to Covid-19: A once-in-a-century pandemic?". The New England Journal of Medicine. 382 (18): 1677–79. doi:10.1056/nejmp2003762. PMID 32109012.
  4. ^ a b 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.
  5. ^ a b c d e f g h Le TT, Cramer JP, Chen R, Mayhew S (October 2020). "Evolution of the COVID-19 vaccine development landscape". Nature Reviews. Drug Discovery. 19 (10): 667–668. doi:10.1038/d41573-020-00151-8. PMID 32887942. S2CID 221503034.
  6. ^ a b c Weintraub R, Yadav P, Berkley S (2 April 2020). "A COVID-19 vaccine will need equitable, global distribution". Harvard Business Review. ISSN 0017-8012. Archived from the original on 9 June 2020. Retrieved 9 June 2020.
  7. ^ a b c "COVID-19 pandemic reveals the risks of relying on private sector for life-saving vaccines, says expert". CBC Radio. 8 May 2020. Archived from the original on 13 May 2020. Retrieved 8 June 2020.
  8. ^ a b c d Ahmed DD (4 June 2020). "Oxford, AstraZeneca COVID-19 deal reinforces 'vaccine sovereignty'". Stat. Archived from the original on 12 June 2020. Retrieved 8 June 2020.
  9. ^ a b Grenfell R, Drew T (14 February 2020). "Here's why the WHO says a coronavirus vaccine is 18 months away". Business Insider. Archived from the original on 5 December 2020. Retrieved 11 November 2020.
  10. ^ Offit P (13 February 2021). "TWiV 720: With vaccines, Offit is on it". This Week in Virology Podcast. Vincent Racaniello Youtube Channel. Archived from the original on 25 May 2021. Retrieved 14 July 2021.
  11. ^ a b c d e f "Update on WHO Solidarity Trial – Accelerating a safe and effective COVID-19 vaccine". World Health Organization (WHO). 27 April 2020. Archived from the original on 30 April 2020. Retrieved 2 May 2020. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable. To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. [The] WHO is working to ensure that all of them have the chance of being tested at the initial stage of development. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale.
  12. ^ a b c Yamey G, Schäferhoff M, Hatchett R, Pate M, Zhao F, McDade KK (May 2020). "Ensuring global access to COVID‑19 vaccines". Lancet. 395 (10234): 1405–06. doi:10.1016/S0140-6736(20)30763-7. PMC 7271264. PMID 32243778. CEPI estimates that developing up to three vaccines in the next 12–18 months will require an investment of at least US$2 billion. This estimate includes Phase 1 clinical trials of eight vaccine candidates, progression of up to six candidates through Phase 2 and 3 trials, completion of regulatory and quality requirements for at least three vaccines, and enhancing global manufacturing capacity for three vaccines.
  13. ^ a b "WHO 'backed China's emergency use' of experimental Covid-19 vaccines". South China Morning Post. 25 September 2020. Archived from the original on 26 September 2020. Retrieved 26 September 2020.
  14. ^ a b Kramer AE (19 September 2020). "Russia Is Slow to Administer Virus Vaccine Despite Kremlin's Approval". The New York Times. ISSN 0362-4331. Archived from the original on 27 September 2020. Retrieved 28 September 2020.
  15. ^ a b "Pfizer and BioNTech to Submit Emergency Use Authorization Request Today to the U.S. FDA for COVID-19 Vaccine". Pfizer (Press release). 20 November 2020. Archived from the original on 29 January 2021. Retrieved 20 November 2020.
  16. ^ a b Park A (20 November 2020). "Exclusive: Pfizer CEO Discusses Submitting the First COVID-19 Vaccine Clearance Request to the FDA". Time. Archived from the original on 29 January 2021. Retrieved 20 November 2020.
  17. ^ a b "Information for Healthcare Professionals on Pfizer/BioNTech COVID-19 vaccine". Medicines & Healthcare products Regulatory Agency (MHRA). 8 December 2020. Archived from the original on 15 March 2021. Retrieved 13 December 2020.
  18. ^ a b "Conditions of Authorisation for Pfizer/BioNTech COVID-19 vaccine". Medicines and Healthcare products Regulatory Agency (MHRA). 3 December 2020. Archived from the original on 26 February 2021. Retrieved 19 December 2020.
  19. ^ a b "UK medicines regulator gives approval for first UK COVID-19 vaccine". Medicines and Healthcare Products Regulatory Agency, Government of the UK. 2 December 2020. Archived from the original on 17 March 2021. Retrieved 2 December 2020.
  20. ^ a b Mueller B (2 December 2020). "U.K. Approves Pfizer Coronavirus Vaccine, a First in the West". The New York Times. Archived from the original on 28 January 2021. Retrieved 2 December 2020.
  21. ^ a b 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.
  22. ^ a b c "Questions and Answers: COVID-19 vaccination in the EU". European Commission. 21 December 2020. Archived from the original on 29 January 2021. Retrieved 21 December 2020.
  23. ^ a b "Bahrain second in the world to approve the Pfizer/BioNTech Covid-19 vaccine". Bahrain News Agency. 4 December 2020. Archived from the original on 17 December 2020. Retrieved 9 December 2020.
  24. ^ a b "UAE: Ministry of Health announces 86 per cent vaccine efficacy". Gulf News. Archived from the original on 24 December 2020. Retrieved 9 December 2020.
  25. ^ a b Thomas K, LaFraniere S, Weiland N, Goodnough A, Haberman M (12 December 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 12 December 2020.
  26. ^ a b c "FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine". U.S. Food and Drug Administration (FDA) (Press release). Archived from the original on 17 March 2021. Retrieved 18 December 2020.
  27. ^ a b c Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K (January 2021). "The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020" (PDF). MMWR. Morbidity and Mortality Weekly Report. 69 (5152): 1653–56. doi:10.15585/mmwr.mm695152e1. PMC 9191904. PMID 33382675. S2CID 229945697. Archived (PDF) from the original on 9 February 2021. Retrieved 18 January 2021.
  28. ^ a b c Lovelace Jr B (19 December 2020). "FDA approves second Covid vaccine for emergency use as it clears Moderna's for U.S. distribution". CNBC. Archived from the original on 26 January 2021. Retrieved 19 December 2020.
  29. ^ Corum J, Zimmer C (17 December 2020). "How the Oxford-AstraZeneca Vaccine Works". The New York Times. Archived from the original on 5 January 2022. Retrieved 2 May 2021.
  30. ^ Tétrault-Farber M, Vasilyeva G (31 March 2021). "Russia registers world's first COVID-19 vaccine for animals". Reuters. Archived from the original on 17 December 2021. Retrieved 4 April 2021.
  31. ^ "В России зарегистрировали первую в мире вакцину против COVID-19 для животных" [The world's first COVID-19 vaccine for animals was registered in Russia]. TASS (in Russian). Moscow. 31 March 2021. Archived from the original on 19 May 2021. Retrieved 19 May 2021.
  32. ^ MORITSUGU K (26 October 2022). "Afraid of needles? China using inhalable COVID-19 vaccine". AP NEWS. Retrieved 2 November 2022.
  33. ^ a b Hotez PJ, Bottazzi ME (January 2022). "Whole Inactivated Virus and Protein-Based COVID-19 Vaccines". Annual Review of Medicine. 73 (1): 55–64. doi:10.1146/annurev-med-042420-113212. PMID 34637324. S2CID 238747462.
  34. ^ Ye Y, Zhang Q, Wei X, Cao Z, Yuan HY, Zeng DD (February 2022). "Equitable access to COVID-19 vaccines makes a life-saving difference to all countries". Nature Human Behaviour. 6 (2): 207–216. doi:10.1038/s41562-022-01289-8. PMC 8873023. PMID 35102361.
  35. ^ a b c Gouglas D, Thanh Le T, Henderson K, Kaloudis A, Danielsen T, Hammersland NC, Robinson JM, Heaton PM, Røttingen JA (December 2018). "Estimating the cost of vaccine development against epidemic infectious diseases: a cost minimisation study". Lancet Global Health. 6 (12): e1386–96. doi:10.1016/S2214-109X(18)30346-2. PMC 7164811. PMID 30342925.
  36. ^ DiMasi JA, Grabowski HG, Hansen RW (May 2016). "Innovation in the pharmaceutical industry: New estimates of R&D costs". Journal of Health Economics. 47: 20–33. doi:10.1016/j.jhealeco.2016.01.012. hdl:10161/12742. PMID 26928437.
  37. ^ "G20 launches initiative for health tools needed to combat the coronavirus". 25 April 2020.
  38. ^ "Access to COVID-19 Tools (ACT) Accelerator" (PDF). World Health Organization (WHO). 24 April 2020.
  39. ^ Moon S, Armstrong J, Hutler B, Upshur R, Katz R, Atuire C, Bhan A, Emanuel E, Faden R, Ghimire P, Greco D (29 January 2022). "Governing the Access to COVID-19 Tools Accelerator: towards greater participation, transparency, and accountability". The Lancet. 399 (10323): 487–494. doi:10.1016/S0140-6736(21)02344-8. ISSN 0140-6736. PMC 8797025. PMID 34902308.
  40. ^ Abedi M (23 March 2020). "Canada to spend $192M on developing COVID-19 vaccine". Global News. Archived from the original on 9 April 2020. Retrieved 24 March 2020.
  41. ^ "Government of Canada funds 49 additional COVID-19 research projects – Details of the funded projects". Government of Canada. 23 March 2020. Archived from the original on 22 March 2020. Retrieved 23 March 2020.
  42. ^ "Government of Canada's research response to COVID-19". Government of Canada. 23 April 2020. Archived from the original on 13 May 2020. Retrieved 4 May 2020.
  43. ^ Aiello R (4 May 2020). "'A global challenge': PM Trudeau commits $850 million to global fight against COVID-19". CTV News. Archived from the original on 10 May 2020. Retrieved 4 May 2020.
  44. ^ a b c d Steenhuysen J, Eisler P, Martell A, Nebehay S (27 April 2020). "Special Report: Countries, companies risk billions in race for coronavirus vaccine". Reuters. Archived from the original on 15 May 2020. Retrieved 2 May 2020.
  45. ^ a b c d Sanger DE, Kirkpatrick DD, Zimmer C, Thomas K, Wee SL (2 May 2020). "With Pressure Growing, Global Race for a Vaccine Intensifies". The New York Times. ISSN 0362-4331. Archived from the original on 11 May 2020. Retrieved 2 May 2020.
  46. ^ Takada N, Satake M (2 May 2020). "US and China unleash wallets in race for coronavirus vaccine". Nikkei Asian Review. Archived from the original on 10 May 2020. Retrieved 3 May 2020.
  47. ^ Talmazan Y, Simmons K, Saravia L (18 May 2020). "China's Xi announces $2B for coronavirus response as WHO faces calls for investigation". NBC News. Archived from the original on 18 May 2020. Retrieved 18 May 2020.
  48. ^ Ore D (23 July 2020). "Mexico says China plans $1 billion loan to ease Latam access to virus vaccine". Reuters. Archived from the original on 25 September 2020. Retrieved 16 August 2020.
  49. ^ "China promises Mekong neighbours access to Chinese Covid-19 vaccine". South China Morning Post. 24 August 2020. Archived from the original on 25 September 2020. Retrieved 24 August 2020.
  50. ^ Morriss E (22 April 2020). "Government launches coronavirus vaccine taskforce as human clinical trials start". Pharmafield. Archived from the original on 26 June 2020. Retrieved 3 May 2020.
  51. ^ Gartner A, Roberts L (3 May 2020). "How close are we to a coronavirus vaccine? Latest news on UK trials". The Telegraph. ISSN 0307-1235. Archived from the original on 4 May 2020. Retrieved 3 May 2020.
  52. ^ "Landmark partnership announced for development of COVID-19 vaccine". University of Oxford. 30 April 2020. Archived from the original on 13 May 2020. Retrieved 3 May 2020.
  53. ^ a b Kuznia R, Polglase K, Mezzofiore G (1 May 2020). "In quest for vaccine, US makes 'big bet' on company with unproven technology". CNN. Archived from the original on 13 May 2020. Retrieved 2 May 2020.
  54. ^ Lee CE, Welker K, Perlmutter-Gumbiner E (1 May 2020). "Health officials eyeing at least one of 14 potential coronavirus vaccines to fast-track". NBC News. Archived from the original on 11 May 2020. Retrieved 2 May 2020.
  55. ^ Cohen J (15 May 2020). "U.S. 'Warp Speed' vaccine effort comes out of the shadows". Science. 368 (6492): 692–93. Bibcode:2020Sci...368..692C. doi:10.1126/science.368.6492.692. ISSN 0036-8075. PMID 32409451.
  56. ^ Sink J, Fabian J, Griffin R (15 May 2020). "Trump introduces 'Warp Speed' leaders to hasten COVID-19 vaccine". Bloomberg. Archived from the original on 21 May 2020. Retrieved 15 May 2020.
  57. ^ Griffith R, Jacobs J (3 June 2020). "White House Works With Seven Drugmakers in 'Warp Speed' Push". Bloomberg. Archived from the original on 3 June 2020. Retrieved 4 June 2020.
  58. ^ "Fact-checking the battle for credit over Pfizer's vaccine announcement". CNN. 10 November 2020. Archived from the original on 16 November 2020. Retrieved 13 November 2020. Pfizer is one of various vaccine manufacturers participating in Operation Warp Speed as a supplier of a potential COVID-19 vaccine," Castillo said in an email. "While Pfizer did reach an advanced purchase agreement with the U.S. government, the company did not accept (Biomedical Advanced Research and Development Authority) funding for the research and development process. All the investment for R&D was made by Pfizer at risk. Dr. Jansen was emphasizing that last point.
  59. ^ McGrail S (15 April 2020). "Sanofi, GSK partner to develop adjuvanted COVID-19 vaccine". PharmaNewsIntelligence. Archived from the original on 9 May 2020. Retrieved 4 May 2020.
  60. ^ Blankenship K (4 June 2020). "AstraZeneca unveils massive $750M deal in effort to produce billions of COVID-19 shots". FiercePharma. Archived from the original on 10 June 2020. Retrieved 8 June 2020.
  61. ^ a b Cohen J (4 June 2020). "Top U.S. scientists left out of White House selection of COVID-19 vaccine short list". Science. doi:10.1126/science.abd1719. ISSN 0036-8075.
  62. ^ Schmidt C (1 June 2020). "Genetic Engineering Could Make a COVID-19 Vaccine in Months Rather Than Years". Scientific American. Archived from the original on 11 October 2020. Retrieved 26 August 2020.
  63. ^ a b 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.
  64. ^ Fox C, Kelion L (16 July 2020). "Russian spies 'target coronavirus vaccine'". BBC News. Archived from the original on 11 October 2020. Retrieved 1 August 2020.
  65. ^ a b Coronavirus: North Korea and Russia hackers 'targeting vaccine' Archived 17 December 2021 at the Wayback Machine, (13 November 2020).
  66. ^ a b North Korea accused of hacking Pfizer for Covid-19 vaccine data Archived 24 April 2022 at the Wayback Machine, BBC News (16 February 2021).
  67. ^ "Public statement for collaboration on COVID-19 vaccine development". World Health Organization (WHO). 13 April 2020. Archived from the original on 20 April 2020. Retrieved 20 April 2020.
  68. ^ a b "Clinical Development Success Rates 2006–2015" (PDF). BIO Industry Analysis. June 2016. Archived (PDF) from the original on 12 September 2019. Retrieved 23 March 2020.
  69. ^ Pandamooz S, Jurek B, Meinung CP, Baharvand Z, Sahebi Shahem-abadi A, Haerteis S, Miyan JA, Downing J, Dianatpour M, Borhani-Haghighi A, Salehi MS (6 January 2022). "Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments". Annual Review of Pharmacology and Toxicology. 62 (1): 25–53. doi:10.1146/annurev-pharmtox-121120-012309. ISSN 0362-1642. PMID 33606962. S2CID 231970935.
  70. ^ a b c d e Diamond MS, Pierson TC (May 2020). "The Challenges of Vaccine Development against a New Virus during a Pandemic". Cell Host & Microbe. 27 (5): 699–703. doi:10.1016/j.chom.2020.04.021. PMC 7219397. PMID 32407708.
  71. ^ Thorp HH (March 2020). "Underpromise, overdeliver". Science. 367 (6485): 1405. Bibcode:2020Sci...367.1405T. doi:10.1126/science.abb8492. PMID 32205459.
  72. ^ Blackwell T (20 April 2020). "COVID-19 vaccine researchers say pandemic lockdown placing many serious obstacles to their work". National Post. Archived from the original on 23 April 2020. Retrieved 3 May 2020.
  73. ^ Chen J (4 May 2020). "Covid-19 has shuttered labs. It could put a generation of researchers at risk". Stat. Archived from the original on 6 May 2020. Retrieved 4 May 2020.
  74. ^ a b c Iwasaki A, Yang Y (June 2020). "The potential danger of suboptimal antibody responses in COVID-19". Nature Reviews. Immunology. 20 (6): 339–341. doi:10.1038/s41577-020-0321-6. PMC 7187142. PMID 32317716.
  75. ^ Lambert PH, Ambrosino DM, Andersen SR, Baric RS, Black SB, Chen RT, Dekker CL, Didierlaurent AM, Graham BS, Martin SD, Molrine DC, Perlman S, Picard-Fraser PA, Pollard AJ, Qin C, Subbarao K, Cramer JP (June 2020). "Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines". Vaccine. 38 (31): 4783–4791. doi:10.1016/j.vaccine.2020.05.064. PMC 7247514. PMID 32507409.
  76. ^ a b Haynes BF, Corey L, Fernandes P, Gilbert PB, Hotez PJ, Rao S, Santos MR, Schuitemaker H, Watson M, Arvin A (4 November 2020). "Prospects for a safe COVID-19 vaccine". Science Translational Medicine. 12 (568): eabe0948. doi:10.1126/scitranslmed.abe0948. ISSN 1946-6242. PMID 33077678. S2CID 224809822.
  77. ^ Hackethal V (16 March 2021). "Why ADE Hasn't Been a Problem With COVID Vaccines". www.medpagetoday.com. Archived from the original on 25 June 2021. Retrieved 1 July 2021.
  78. ^ "Draft landscape of COVID 19 candidate vaccines". World Health Organization (WHO). 10 December 2020. Archived from the original on 30 April 2020. Retrieved 11 December 2020.
  79. ^ a b c d "An international randomised trial of candidate vaccines against COVID-19: Outline of Solidarity vaccine trial" (PDF). World Health Organization (WHO). 9 April 2020. Archived (PDF) from the original on 12 May 2020. Retrieved 9 May 2020.
  80. ^ a b "Vaccine Safety – Vaccines". vaccines.gov. US Department of Health and Human Services. Archived from the original on 22 April 2020. Retrieved 13 April 2020.
  81. ^ a b c "The drug development process". U.S. Food and Drug Administration (FDA). 4 January 2018. Archived from the original on 22 February 2020. Retrieved 12 April 2020.
  82. ^ a b c d e Cohen J (June 2020). "Pandemic vaccines are about to face the real test". Science. 368 (6497): 1295–1296. Bibcode:2020Sci...368.1295C. doi:10.1126/science.368.6497.1295. PMID 32554572.
  83. ^ "How flu vaccine effectiveness and efficacy are measured". Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, US Department of Health and Human Services. 29 January 2016. Archived from the original on 7 May 2020. Retrieved 6 May 2020.
  84. ^ "Principles of epidemiology, Section 8: Concepts of disease occurrence". Centers for Disease Control and Prevention, Center for Surveillance, Epidemiology, and Laboratory Services, US Department of Health and Human Services. 18 May 2012. Archived from the original on 6 April 2020. Retrieved 6 May 2020.
  85. ^ a b AstraZeneca (12 April 2021). "A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults, to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19". Iqvia Pty Ltd. Archived from the original on 23 August 2020. Retrieved 11 June 2021.
  86. ^ Covid news live: England drops all ‘plan B’ restrictions; Moderna begins trial of Omicron-specific booster shot Archived 29 January 2022 at the Wayback Machine The Guardian
  87. ^ Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger J (August 2013). "Vaccine hesitancy: an overview". Human Vaccines & Immunotherapeutics. 9 (8): 1763–73. doi:10.4161/hv.24657. PMC 3906279. PMID 23584253.
  88. ^ Howard J, Stracqualursi V (18 June 2020). "Fauci warns of 'anti-science bias' being a problem in US". CNN. Archived from the original on 21 June 2020. Retrieved 21 June 2020.
  89. ^ Winter SS, Page-Reeves JM, Page KA, Haozous E, Solares A, Nicole Cordova C, Larson RS (May 2018). "Inclusion of special populations in clinical research: important considerations and guidelines". Journal of Clinical and Translational Research (Review). 4 (1): 56–69. PMC 6410628. PMID 30873495.
  90. ^ a b Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Odondi L, Sydes MR, Villar SS, Wason JM, Weir CJ, Wheeler GM, Yap C, Jaki T (February 2018). "Adaptive designs in clinical trials: why use them, and how to run and report them". BMC Medicine. 16 (1): 29. doi:10.1186/s12916-018-1017-7. PMC 5830330. PMID 29490655.
  91. ^ "Adaptive designs for clinical trials of drugs and biologics: Guidance for industry" (PDF). U.S. Food and Drug Administration (FDA). 1 November 2019. Archived from the original on 13 December 2019. Retrieved 3 April 2020.
  92. ^ Lambkin-Williams R, Noulin N, Mann A, Catchpole A, Gilbert AS (June 2018). "The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics". Respiratory Research. 19 (1): 123. doi:10.1186/s12931-018-0784-1. PMC 6013893. PMID 29929556.
  93. ^ a b Eyal N, Lipsitch M, Smith PG (May 2020). "Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure". The Journal of Infectious Diseases. 221 (11): 1752–1756. doi:10.1093/infdis/jiaa152. PMC 7184325. PMID 32232474.
  94. ^ a b c Callaway E (April 2020). "Should scientists infect healthy people with the coronavirus to test vaccines?". Nature. 580 (7801): 17. Bibcode:2020Natur.580...17C. doi:10.1038/d41586-020-00927-3. PMID 32218549.
  95. ^ a b Cohen J (31 March 2020). "Speed coronavirus vaccine testing by deliberately infecting volunteers? Not so fast, some scientists warn". Science. doi:10.1126/science.abc0006.
  96. ^ "Key criteria for the ethical acceptability of COVID-19 human challenge studies" (PDF). World Health Organization (WHO). 6 May 2020. Archived (PDF) from the original on 8 May 2020. Retrieved 12 May 2020.
  97. ^ a b Callaway E (October 2020). "Dozens to be deliberately infected with coronavirus in UK 'human challenge' trials". Nature. 586 (7831): 651–652. Bibcode:2020Natur.586..651C. doi:10.1038/d41586-020-02821-4. PMID 33082550. S2CID 224823112.
  98. ^ a b "WHO publishes Emergency Use Listing procedure and roadmap to make new medical products more readily available during health emergencies" (Press release). World Health Organization (WHO). 9 January 2020. Archived from the original on 29 September 2020. Retrieved 23 August 2020.
  99. ^ "Vaccines: The Emergency Authorisation Procedure". European Medicines Agency. 2020. Archived from the original on 24 September 2020. Retrieved 21 August 2020.
  100. ^ Byrne J (19 October 2020). "Moderna COVID-19 vaccine under rolling review process in Canada, EU". BioPharma-Reporter.com, William Reed Business Media Ltd. Archived from the original on 25 February 2021. Retrieved 25 November 2020.
  101. ^ Dangerfield K (20 November 2020). "Pfizer files for emergency use of coronavirus vaccine in U.S. – what about in Canada?". Global News. Archived from the original on 25 January 2021. Retrieved 25 November 2020.
  102. ^ "Coronavirus: UAE authorises emergency use of vaccine for frontline workers". The National. 14 September 2020. Archived from the original on 2 January 2020. Retrieved 18 November 2020.
  103. ^ Barrington L (3 November 2020). "Bahrain latest country to vaccinate frontline workers with COVID-19 shot". Reuters. Archived from the original on 30 December 2021. Retrieved 18 November 2020.
  104. ^ a b "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. Public Domain This article incorporates text from this source, which is in the public domain.
  105. ^ Malik AA, McFadden SM, Elharake J, Omer SB (September 2020). "Determinants of COVID-19 vaccine acceptance in the US". eClinicalMedicine. 26: 100495. doi:10.1016/j.eclinm.2020.100495. PMC 7423333. PMID 32838242.
  106. ^ "FDA may be risk-averse to grant emergency use for a Covid-19 vaccine; political pressure and hazy EUA standards are factors". ClinicalTrials Arena, Verdict Media, Ltd. 2 July 2020. Archived from the original on 22 July 2020. Retrieved 22 August 2020.
  107. ^ Hoffman J (18 July 2020). "Mistrust of a coronavirus vaccine could imperil widespread immunity". The New York Times. Archived from the original on 27 September 2020. Retrieved 23 August 2020.
  108. ^ "Biopharma Leaders Unite to Stand with Science" (Press release). 8 September 2020. Archived from the original on 1 January 2021. Retrieved 31 December 2020 – via Business Wire.
  109. ^ "Covid-19 vaccine: Margaret Keenan 'so privileged' to get first jab". BBC News Online. 8 December 2020. Archived from the original on 8 December 2020. Retrieved 8 December 2020.
  110. ^ Mueller B (8 December 2020). "As U.K. Begins Vaccinations, a Glimpse of Life After Covid". The New York Times. Archived from the original on 14 December 2020. Retrieved 20 December 2020.
  111. ^ "Covid: Russia begins vaccinations in Moscow". BBC News Online. 5 December 2020. Archived from the original on 1 June 2022. Retrieved 18 January 2021.
  112. ^ Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K (December 2020). "The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine – United States, December 2020" (PDF). MMWR. Morbidity and Mortality Weekly Report. 69 (50): 1922–24. doi:10.15585/mmwr.mm6950e2. PMC 7745957. PMID 33332292. Archived (PDF) from the original on 19 December 2020. Retrieved 18 January 2021.
  113. ^ "Swissmedic grants authorisation for the first COVID-19 vaccine in Switzerland" (Press release). Swiss Agency for Therapeutic Products (Swissmedic). 19 December 2020. Archived from the original on 10 January 2021. Retrieved 19 December 2020.
  114. ^ "COVID-19: Switzerland can start vaccinating vulnerable groups already in December" (Press release). Swiss Federal Office of Public Health. 19 December 2020. Archived from the original on 9 January 2021. Retrieved 19 December 2020.
  115. ^ Pralong J (23 December 2020). "La piqûre de l'espoir pratiquée à Lucerne". Heidi.news. Archived from the original on 10 January 2021. Retrieved 23 December 2020.
  116. ^ Campbell D (16 December 2020). "138,000 people in UK receive Covid vaccine in first week". The Guardian. Archived from the original on 25 March 2022. Retrieved 18 January 2021.
  117. ^ Herper M (15 December 2020). "Inside the frantic and secretive sprint to name the Covid-19 vaccines". Stat. Archived from the original on 17 December 2020. Retrieved 19 December 2020.
  118. ^ Bird S (14 November 2020). "Trademark filings offer tantalising glimpse of coronavirus vaccine's name". The Daily Telegraph. Archived from the original on 12 January 2022. Retrieved 19 December 2020.
  119. ^ "Moderna Applies for Emergency F.D.A. Approval for Its Coronavirus Vaccine". The New York Times. 30 November 2020. Archived from the original on 30 November 2020. Retrieved 30 November 2020.
  120. ^ "Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization". Moderna, Inc. (Press release). 30 November 2020. Archived from the original on 30 November 2020. Retrieved 30 November 2020.
  121. ^ "Oxford University/AstraZeneca vaccine authorised by UK medicines regulator". Gov.uk. Department of Health and Social Care. 30 December 2020. Archived from the original on 16 March 2021. Retrieved 30 December 2020.
  122. ^ "Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca". Medicines and Healthcare products Regulatory Agency (MHRA). 30 December 2020. Archived from the original on 9 March 2021. Retrieved 4 January 2021.
  123. ^ "Conditions of Authorisation for COVID-19 Vaccine AstraZeneca". Medicines and Healthcare products Regulatory Agency (MHRA). 30 December 2020. Archived from the original on 18 February 2021. Retrieved 4 January 2021.
  124. ^ "TGA grants provisional determination for COVID-19 vaccine". Therapeutic Goods Administration (TGA). 9 October 2020. Archived from the original on 29 October 2020. Retrieved 25 October 2020.
  125. ^ "TGA grants second provisional determination for a COVID-19 vaccine". Therapeutic Goods Administration (TGA). 14 October 2020. Archived from the original on 28 October 2020. Retrieved 25 October 2020.
  126. ^ "TGA grants third provisional determination for a COVID-19 vaccine". Therapeutic Goods Administration (TGA). 16 November 2020. Archived from the original on 16 January 2021. Retrieved 19 December 2020.
  127. ^ "Comirnaty". Therapeutic Goods Administration. 25 January 2021. Archived from the original on 1 February 2021. Retrieved 25 January 2021.
  128. ^ "TGA provisionally approves Pfizer COVID-19 vaccine". Therapeutic Goods Administration (TGA) (Press release). 25 January 2021. Archived from the original on 26 January 2021. Retrieved 25 January 2021.
  129. ^ "Comirnaty (BNT162b2 [mRNA]) COVID‑19 Vaccine Product Information" (PDF). Therapeutic Goods Administration (TGA). Archived from the original on 2 February 2021. Retrieved 25 January 2021.
  130. ^ Australian Public Assessment Report for BNT162b2 (mRNA) (PDF) (Report). Therapeutic Goods Administration (TGA). Archived (PDF) from the original on 26 January 2021. Retrieved 25 January 2021.
  131. ^ "Elasomeran". Therapeutic Goods Administration. 24 June 2021. Archived from the original on 27 June 2021. Retrieved 18 August 2021.
  132. ^ "EMA starts first rolling review of a COVID-19 vaccine in the EU" (Press release). European Medicines Agency (EMA). 1 October 2020. Archived from the original on 1 October 2020. Retrieved 1 October 2020.
  133. ^ "COVID-19 vaccines: key facts". European Medicines Agency (EMA). 14 September 2020. Archived from the original on 7 October 2020. Retrieved 1 October 2020.
  134. ^ "EMA starts second rolling review of a COVID-19 vaccine" (Press release). European Medicines Agency (EMA). 5 October 2020. Archived from the original on 6 October 2020. Retrieved 6 October 2020.
  135. ^ "Update on rolling review of AstraZeneca's COVID-19 vaccine" (Press release). European Medicines Agency (EMA). 30 December 2020. Archived from the original on 30 December 2020. Retrieved 30 December 2020.
  136. ^ a b c "EMA publishes safety monitoring plan and guidance on risk management planning for COVID-19 vaccines" (Press release). European Medicines Agency (EMA). 13 November 2020. Archived from the original on 13 November 2020. Retrieved 13 November 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  137. ^ "EMA considerations on COVID-19 vaccine approval". European Medicines Agency (EMA). 19 November 2020. Archived from the original on 19 November 2020. Retrieved 19 November 2020.
  138. ^ "EMA starts rolling review of mRNA COVID-19 vaccine by Moderna Biotech Spain, S.L." (Press release). European Medicines Agency (EMA). 16 November 2020. Archived from the original on 16 November 2020. Retrieved 16 November 2020.
  139. ^ a b "EMA receives application for conditional marketing authorisation of Moderna COVID-19 vaccine" (Press release). European Medicines Agency (EMA). 1 December 2020. Archived from the original on 1 December 2020. Retrieved 1 December 2020.
  140. ^ a b "EMA receives application for conditional marketing authorisation of COVID-19 mRNA vaccine BNT162b2" (Press release). European Medicines Agency (EMA). 1 December 2020. Archived from the original on 1 December 2020. Retrieved 1 December 2020.
  141. ^ "Update on assessment of the BioNTech and Pfizer BNT162b2 vaccine marketing authorisation application" (Press release). European Medicines Agency (EMA). 15 December 2020. Archived from the original on 15 December 2020. Retrieved 15 December 2020.
  142. ^ "Update on assessment of marketing authorisation application for Moderna's mRNA-1273 COVID-19 vaccine" (Press release). European Medicines Agency (EMA). 17 December 2020. Archived from the original on 17 December 2020. Retrieved 17 December 2020.
  143. ^ "EMA starts rolling review of Janssen's COVID-19 vaccine Ad26.COV2.S" (Press release). European Medicines Agency (EMA). 1 December 2020. Archived from the original on 8 January 2021. Retrieved 1 December 2020.
  144. ^ a b "EMA recommends first COVID-19 vaccine for authorisation in the EU" (Press release). European Medicines Agency (EMA). 21 December 2020. Archived from the original on 30 January 2021. Retrieved 21 December 2020.
  145. ^ "Comirnaty EPAR". European Medicines Agency (EMA). 21 December 2020. Archived from the original on 24 January 2022. Retrieved 23 December 2020.
  146. ^ "Statement by President von der Leyen on the marketing authorisation of the BioNTech-Pfizer vaccine against COVID-19". European Commission. Archived from the original on 11 January 2021. Retrieved 21 December 2020.
  147. ^ "Comirnaty". Union Register of medicinal products. Archived from the original on 24 January 2021. Retrieved 29 January 2021.
  148. ^ a b Cavaleri M, Enzmann H, Straus S, Cooke E (January 2021). "The European Medicines Agency's EU conditional marketing authorisations for COVID-19 vaccines". Lancet. 397 (10272): 355–357. doi:10.1016/s0140-6736(21)00085-4. ISSN 0140-6736. PMC 7833511. PMID 33453149.
  149. ^ "COVID-19 Vaccine Moderna EPAR". European Medicines Agency (EMA). 4 January 2021. Archived from the original on 12 March 2021. Retrieved 20 January 2021.
  150. ^ "EMA recommends COVID-19 Vaccine Moderna for authorisation in the EU" (Press release). European Medicines Agency. 6 January 2021. Archived from the original on 17 March 2021. Retrieved 6 January 2021.
  151. ^ "European Commission authorises second safe and effective vaccine against COVID-19". European Commission (Press release). Archived from the original on 20 January 2021. Retrieved 6 January 2021.
  152. ^ "COVID-19 Vaccine Moderna". Union Register of medicinal products. Archived from the original on 24 January 2021. Retrieved 14 January 2021.
  153. ^ "EMA receives application for conditional marketing authorisation of COVID-19 Vaccine AstraZeneca". European Medicines Agency (EMA). 12 January 2021. Archived from the original on 30 March 2021. Retrieved 12 January 2021.
  154. ^ "COVID-19 Vaccine AstraZeneca". European Medicines Agency (EMA). 28 January 2021. Archived from the original on 16 February 2021. Retrieved 29 January 2021.
  155. ^ "EMA recommends COVID-19 Vaccine AstraZeneca for authorisation in the EU" (Press release). European Medicines Agency (EMA). 29 January 2021. Archived from the original on 9 February 2021. Retrieved 29 January 2021.
  156. ^ "European Commission authorises third safe and effective vaccine against COVID-19". European Commission (Press release). Archived from the original on 10 February 2021. Retrieved 29 January 2021.
  157. ^ "COVID-19 Vaccine AstraZeneca". Union Register of medicinal products. Archived from the original on 26 March 2021. Retrieved 29 January 2021.
  158. ^ "EMA starts rolling review of Novavax's COVID-19 vaccine (NVX-CoV2373)". European Medicines Agency (EMA). 3 February 2021. Archived from the original on 2 July 2021. Retrieved 3 February 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  159. ^ "EMA starts rolling review of CureVac's COVID-19 vaccine (CVnCoV)" (Press release). European Medicines Agency (EMA). 11 February 2021. Archived from the original on 12 February 2021. Retrieved 12 February 2021.
  160. ^ "EMA preparing guidance to tackle COVID-19 variants" (Press release). European Medicines Agency (EMA). 10 February 2021. Archived from the original on 15 February 2021. Retrieved 10 February 2021.
  161. ^ "EMA receives application for conditional marketing authorisation of COVID-19 Vaccine Janssen". European Medicines Agency (EMA). 16 February 2021. Archived from the original on 16 February 2021. Retrieved 16 February 2021.
  162. ^ "COVID-19 Vaccine Janssen EPAR". European Medicines Agency (EMA). 5 March 2021. Archived from the original on 15 March 2021. Retrieved 11 July 2021.
  163. ^ "EMA recommends COVID-19 Vaccine Janssen for authorisation in the EU". European Medicines Agency (EMA) (Press release). 11 March 2021. Archived from the original on 11 March 2021. Retrieved 11 July 2021.
  164. ^ "European Commission authorises fourth safe and effective vaccine against COVID-19". European Commission (Press release). Archived from the original on 25 August 2020. Retrieved 11 July 2021.
  165. ^ a b "EMA starts rolling review of the Sputnik V COVID-19 vaccine" (Press release). European Medicines Agency (EMA). 4 March 2021. Archived from the original on 4 March 2021. Retrieved 4 March 2021.
  166. ^ "EMA starts evaluating use of COVID-19 vaccine Comirnaty in young people aged 12 to 15". European Medicines Agency (EMA) (Press release). 3 May 2021. Archived from the original on 7 May 2021. Retrieved 7 May 2021.
  167. ^ a b "EMA starts rolling review of COVID-19 Vaccine (Vero Cell) Inactivated". European Medicines Agency (EMA) (Press release). 4 May 2021. Archived from the original on 4 May 2021. Retrieved 7 May 2021.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=History_of_COVID-19_vaccine_development&oldid=1235147233"