125-673: The Moderna COVID‑19 vaccine , sold under the brand name Spikevax , is a COVID-19 vaccine developed by the American company Moderna , the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA). Depending on the jurisdiction, it is authorized for use in humans aged six months, twelve years, or eighteen years and older. It provides protection against COVID-19 , which
250-435: A PEGylated lipid nanoparticle drug delivery (LNP) system. Once the compound is inside a human cell, the mRNA links up with the cell's endoplasmic reticulum . The mRNA-1273 is encoded to trigger the cell into making a specific protein using the cell's normal manufacturing process. The vaccine encodes a version of the spike protein with a modification called 2P, in which the protein includes two stabilizing mutations in which
375-475: A phase III clinical trial using two 100-μg doses administered 29 days apart. In July 2020, Moderna announced in a preliminary report that its Operation Warp Speed candidate had led to production of neutralizing antibodies in healthy adults in phase I clinical testing . "At the 100-microgram dose, the one Moderna is advancing into larger trials, all 15 patients experienced side effects, including fatigue, chills, headache, muscle pain, and pain at
500-417: A three prime untranslated region (bases 3880–4174) combined from AES and mtRNR1 selected for increased protein expression and mRNA stability and a poly(A) tail comprising 30 adenosine residues, a 10-nucleotide linker sequence, and 70 other adenosine residues (bases 4175–4284). The sequence contains no uridine residues; they are replaced by 1-methyl-3'-pseudouridylyl . The 2P proline substitutions in
625-400: A 15-minute observation period after injection. Delayed cutaneous reactions at injection sites resulting in rash-like erythemas have also been observed in rare cases but are not considered serious or contraindications to subsequent vaccination. The incidence rate for local adverse erythema is about 10.8%. In 1.9% of cases, redness may extend to a size of 100 mm or greater. In June 2021,
750-503: A COVID‑19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID‑19 infection in vaccinated individuals. Adjuvants used in COVID‑;19 vaccine formulation may be particularly effective for technologies using the inactivated COVID‑19 virus and recombinant protein-based or vector-based vaccines. Aluminum salts, known as " alum ", were the first adjuvant used for licensed vaccines and are
875-664: A booster for use in the UK. The same month, the European Union authorized both the BA.1 and the BA.4/BA.5 (tozinameran/famtozinameran) booster versions of the bivalent vaccine. In August 2024, the FDA approved and granted emergency authorization for a monovalent Omicron KP.2 version of the Pfizer–BioNTech COVID-19 vaccine. The approval of Comirnaty (COVID-19 Vaccine, mRNA) (2024-2025 Formula)
1000-485: A clinical trial conducted in more than 2,200 children aged 5–11 has generated a "robust" response and is safe. In Phase III trials for the vaccine, there were no safety concerns and few adverse events. Most side effects of the Pfizer–BioNTech COVID‑;19 vaccine are mild to moderate in severity, and are gone within a few days. They are similar to other adult vaccines and are normal signs that
1125-460: A decade to develop. In contrast, mRNA is a molecule that can be made quickly, and research on mRNA to fight diseases was begun decades before the COVID‑19 pandemic by scientists such as Drew Weissman and Katalin Karikó , who tested on mice. Moderna began human testing of an mRNA vaccine in 2015. Viral vector vaccines were also developed for the COVID‑19 pandemic after the technology
1250-585: A documented history of allergies or allergic reactions. The UK's Medicines and Healthcare products Regulatory Agency (MHRA) advised on 9 December 2020 that people who have a history of "significant" allergic reaction should not receive the Pfizer–BioNTech COVID‑19 vaccine. On 12 December, the Canadian regulator followed suit, noting that: "Both individuals in the U.K. had a history of severe allergic reactions and carried adrenaline auto injectors. They both were treated and have recovered." In June 2021,
1375-434: A few days. Common side effects include mild to moderate pain at the injection site, fatigue , and headaches . Reports of serious side effects, such as allergic reactions, remain very rare with no long-term complications documented. The vaccine is the first COVID‑19 vaccine to be authorized by a stringent regulatory authority for emergency use and the first to be approved for regular use. In December 2020,
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#17328760202211500-425: A partnership with Swiss vaccine manufacturer Lonza Group , to supply 300 million doses per annum. In May 2020, Moderna began a phase IIa clinical trial recruiting six hundred adult participants to assess safety and differences in antibody response to two doses of its candidate vaccine, mRNA-1273, a study expected to complete in 2021. In July 2020, Moderna scientists published preliminary results of
1625-588: A preliminary study, the U.S. Centers for Disease Control and Prevention (CDC) recommends that pregnant women get vaccinated with the COVID‑19 vaccine. A statement by the British Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) reported that the two agencies had reached a conclusion that the vaccine is safe and effective in children aged between 12 and 15 years. In May 2021, experts commissioned by
1750-850: A robust T-cell response and their genes are more conserved and recombine less frequently (compared to Spike). Future generations of COVID‑19 vaccines that may target more conserved genomic regions will also act as insurance against the manifestation of catastrophic scenarios concerning the future evolutionary path of SARS-CoV-2, or any similar coronavirus epidemic/pandemic. Platforms developed in 2020 involved nucleic acid technologies ( nucleoside-modified messenger RNA and DNA ), non-replicating viral vectors , peptides , recombinant proteins , live attenuated viruses , and inactivated viruses . Many vaccine technologies being developed for COVID‑19 are not like influenza vaccines but rather use "next-generation" strategies for precise targeting of COVID‑19 infection mechanisms. Several of
1875-474: A second intranasal vaccine as a booster, trade name Pneucolin . Aivita Biomedical is developing an experimental autologous dendritic cell COVID‑19 vaccine kit where the vaccine is prepared and incubated at the point-of-care using cells from the intended recipient. The vaccine is undergoing small phase I and phase II clinical studies. A universal coronavirus vaccine would be effective against all coronaviruses and possibly other viruses. The concept
2000-607: A similar level of neutralizing antibodies against the Omicron variant as seen after two doses against other variants. In December 2021, private health insurer Discovery Health , in collaboration with the South African Medical Research Council , reported that real-world data from more than 211,000 cases of COVID-19 in South Africa, of which 78,000 were of the Omicron variant , indicate that effectiveness against
2125-505: A spike ferritin-based nanoparticle (SpFN). This vaccine began a Phase I clinical trial in April 2022. Results of this trial were published in May 2024. Other universal vaccines that have entered clinical trial include OVX033 (France), PanCov (France), pEVAC-PS (UK), and VBI-2902 (Canada). Another strategy is to attach vaccine fragments from multiple strains to a nanoparticle scaffold. One theory
2250-465: A standard medical refrigerator of 2–8 °C (36–46 °F) for up to thirty days or −20 °C (−4 °F) for up to four months, whereas the Pfizer-BioNTech candidate requires ultracold freezer storage between −80 and −60 °C (−112 and −76 °F). Low-income countries usually have cold chain capacity for only standard refrigerator storage, not ultracold freezer storage. In February 2021,
2375-550: A three-stage process. The first stage involves the molecular cloning of DNA plasmids that code for the spike protein by infusing them into Escherichia coli bacteria. For all markets, this stage is conducted in the United States, at a small Pfizer pilot plant in Chesterfield, Missouri (near St. Louis ). After four days of growth, the bacteria are killed and broken open , and the contents of their cells are purified over
2500-562: A week and a half to recover the desired DNA product. The DNA is bottled and frozen for shipment. Safely and quickly transporting the DNA at this stage is so important that Pfizer has used its company jet and helicopter to assist. The second stage is being conducted at a Pfizer plant in Andover, Massachusetts , in the United States, and at BioNTech's plants in Germany. The DNA is used as a template to build
2625-440: Is an mRNA sequence containing a total of 4101 nucleotides that encodes the full-length SARS-CoV-2 spike (S) glycoprotein, with two mutations (K986P and V987P) designed to stabilize the pre-fusion conformation. The sequence is further optimized by: A putative sequence of the vaccine has been published on a forum for professional virologists, obtained by direct sequencing of residual vaccine material in used vials. The vaccine mRNA
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#17328760202212750-499: Is authorized for use in humans to provide protection against COVID-19 , caused by infection with the SARS-CoV-2 virus . The vaccine is given by intramuscular injection . It is composed of nucleoside-modified mRNA (modRNA) that encodes a mutated form of the full-length spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles . Initial guidance recommended a two-dose regimen, given 21 days apart; this interval
2875-458: Is caused by infection by the SARS-CoV-2 virus. It is designed to be administered in two or three 0.5- mL doses given by intramuscular injection , primarily into the deltoid muscle, at an interval of at least 28 days apart. The World Health Organization advises an eight-week interval between doses to optimize efficacy. Additional booster doses are approved in some regions to maintain immunity. Clinical trials and real-world data have demonstrated
3000-438: Is dissolved in an aqueous buffer containing tromethamine , tromethamine hydrochloride , sodium acetate , and sucrose . The mRNA is encapsulated in lipid nanoparticles that stabilize the mRNA and facilitate its entry into cells. The nanoparticles are manufactured from the following lipids : Moderna is relying extensively on contract manufacturing organizations to scale up its vaccine manufacturing process. The first step of
3125-469: Is encapsulated in lipid nanoparticles . In August and September 2022, bivalent versions of the vaccine (Moderna COVID-19 Vaccine, Bivalent) containing elasomeran/elasomeran 0-omicron (Spikevax Bivalent Zero/Omicron) were authorized for use as booster doses in individuals aged 18 or older in the United Kingdom, Switzerland, Australia, Canada, the European Union, and the United States. The second component of
3250-483: Is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval . Effectiveness is generally expected to slowly decrease over time. In November 2021, Public Health England reported a possible but extremely small reduction in effectiveness against symptomatic disease from the Delta sublineage AY.4.2 at longer intervals after the second dose. Preliminary data suggest that
3375-682: Is preferable, and partial doses within a vial should be discarded. The Italian Medicines Agency officially authorized the use of excess doses remaining within single vials. The Danish Health Authority allows mixing partial doses from two vials. As of 8 January 2021, each vial contains six doses. In the United States, vials will be counted as five doses when accompanied by regular syringes and as six doses when accompanied by low dead space syringes. The vaccine can be stored at 2 to 8 °C (36 to 46 °F) for thirty days before use and at 25 °C (77 °F) or 30 °C (86 °F) for up to two hours before use. During distribution
3500-612: Is stable. The study also found that cross-reactive T cells acquired during infection with other coronaviruses that cause the common cold increased the response to the vaccine. Moderna and the National Institute of Allergy and Infectious Diseases began a phase III trial in the US in July 2020, with a plan to enroll and assign thirty-thousand volunteers to two groups – one group receiving two 100-μg doses of mRNA-1273 vaccine and
3625-523: Is supplied in a multidose vial as "a white to off-white, sterile, preservative-free, frozen suspension for intramuscular injection ". It must be thawed to room temperature and diluted with normal saline before administration. The initial course consists of two doses. The World Health Organization (WHO) recommends an interval of three to four weeks between doses. Delaying the second dose by up to twelve weeks increases immunogenicity , even in older adults, against all variants of concern . Authors of
3750-498: Is that a broader range of strains can be vaccinated against by targeting the receptor-binding domain, rather than the whole spike protein . As of September 2020 , eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity. An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen , such as the COVID‑19 virus or influenza virus. Specifically, an adjuvant may be used in formulating
3875-463: Is the first product from Moderna that has been authorized by the FDA. In June 2022, the EUA was expanded to include people aged six months through sixteen years of age. In April 2023, the authorization for the original, monovalent, version of the vaccine in the US was withdrawn. As of April 2023, only the bivalent (Original and Omicron BA.4/BA.5) version of the vaccine is authorized in the US. In December 2020,
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4000-593: Is the same as Convidecia's only dose. In August 2021, the developers of Sputnik V proposed, in view of the Delta case surge, that Pfizer test the Ad26 component (termed its 'Light' version) as a booster shot. Inactivated vaccines consist of virus particles that are grown in culture and then killed using a method such as heat or formaldehyde to lose disease-producing capacity while still stimulating an immune response. Inactivated virus vaccines authorized in China include
4125-527: Is used to provide protection against infection by the SARS‑;CoV‑2 virus in order to prevent COVID‑19. The vaccine is given by intramuscular injection into the deltoid muscle of the arm. The initial course consists of two doses. The World Health Organization (WHO) recommends an interval of eight weeks between doses. A third, fourth, or fifth dose can be added in some countries. Evidence of vaccine efficacy starts about two weeks after
4250-501: The Israel's Ministry of Health announced a probable relationship between the second dose and myocarditis in a small group of 16–30-year-old men. Between December 2020 and May 2021, there were 55 cases of myocarditis per 1 million people vaccinated, 95% of which were classified as mild and most spent no more than four days in the hospital. Since April 2021, increasing number of cases of myocarditis and pericarditis have been reported in
4375-676: The Norwegian Medicines Agency concluded that the Pfizer-BioNTech vaccine is the likely cause of ten deaths of frail elderly patients in Norwegian nursing homes. They said that people with very short life expectancies have little to gain from vaccination, having a real risk of adverse reactions in the last days of life and of dying earlier. A 2021 report by the New South Wales Government ( NSW Health ) in Australia found that
4500-587: The Oxford–AstraZeneca COVID‑19 vaccine , the Sputnik V COVID‑19 vaccine , Convidecia , and the Janssen COVID‑19 vaccine . Convidecia and Janssen are both one-shot vaccines that offer less complicated logistics and can be stored under ordinary refrigeration for several months. Sputnik V uses Ad26 for its first dose, which is the same as Janssen's only dose, and Ad5 for the second dose, which
4625-528: The US Department of Health and Human Services . BARDA funded 100% of the cost of bringing the vaccine to FDA licensure. The United States government provided $ 2.5 billion in total funding for the Moderna COVID‑;19 vaccine (mRNA-1273). Private donors also made contributions to the vaccine's development. The Dolly Parton COVID-19 Research Fund contributed $ 1 million. In March 2020,
4750-413: The nasal mucosa , which is a portal for viral entry into the body. These vaccines are designed to stimulate nasal immune factors , such as IgA . In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (or needle phobia ) are involved. A variety of intranasal COVID‑19 vaccines are undergoing clinical trials. The first authorised intranasal vaccine
4875-625: The phase I human trial of mRNA-1273 began in partnership with the US National Institute of Allergy and Infectious Diseases . In April, the US Biomedical Advanced Research and Development Authority (BARDA) allocated up to $ 483 million for Moderna's vaccine development. Plans for a phase II dosing and efficacy trial to begin in May were approved by the US Food and Drug Administration (FDA). Moderna signed
5000-496: The 95% confidence interval . Effectiveness is generally expected to slowly decrease over time. In August 2021, results from a study suggested that the effectiveness against infection decreased from 91% ( 81 – 96% ) to 66% ( 26 – 84% ) when the Delta variant became predominant in the US, which may be due to unmeasured and residual confounding related to a decline in vaccine effectiveness over time. Limited data are available on
5125-460: The BNT162b2 vaccine is based on use of nucleoside-modified mRNA (modRNA) which encodes a mutated form of the full-length spike protein found on the surface of the SARS-CoV-2 virus, triggering an immune response against infection by the virus protein. The modRNA sequence of the vaccine is 4,284 nucleotides long. It consists of a five-prime cap ; a five prime untranslated region derived from
Moderna COVID-19 vaccine - Misplaced Pages Continue
5250-882: The Chinese CoronaVac and the Sinopharm BIBP and WIBP vaccines; there is also the Indian Covaxin , the Russian CoviVac , the Kazakh vaccine QazVac , and the Iranian COVIran Barekat . Vaccines in clinical trials include the Valneva COVID‑;19 vaccine . Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits , but they can be any molecule fragment of
5375-478: The EMA was based on over 392 million doses administered in the European Union. According to the EMA "the benefits of Comirnaty in preventing COVID‑19 continue to outweigh any risks, and there are no recommended changes regarding the use of this vaccine." Rare side effects (that may affect up to one in 1,000 people) include temporary one sided facial drooping and allergic reactions , such as hives or swelling of
5500-716: The European Union. Authorized vaccines of this type include the Pfizer–BioNTech and Moderna vaccines. The CVnCoV RNA vaccine from CureVac failed in clinical trials. Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID‑19 vaccine administration resulted in 175 cases of severe allergic reactions, of which 21 were anaphylaxis . For 4,041,396 Moderna COVID‑19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported. Lipid nanoparticles (LNPs) were most likely responsible for
5625-502: The Marburg facility also performs the step of combining mRNA with lipids to form lipid nanoparticles, then ships the vaccine in bulk to other facilities for fill and finish (i.e., filling and boxing vials). In April 2021, the EMA authorized an increase in batch size and associated process scale up at Pfizer's plant in Puurs. This increase is expected to have a significant impact on the supply of
5750-603: The Moderna COVID‑19 vaccine was authorized by Health Canada . In January 2021, the Moderna COVID‑19 vaccine was authorized for use in Israel by its Ministry of Health . In February 2021, the Moderna COVID‑19 vaccine was authorized for use in Singapore by its Health Sciences Authority . COVID-19 vaccine A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ),
5875-456: The Moderna COVID‑19 vaccine was under evaluation for emergency authorization or approval by multiple countries which would enable rapid rollout of the vaccine in the United Kingdom, the European Union (EU), Canada, and the United States. In December 2020, the Moderna COVID‑19 vaccine was authorized by the US Food and Drug Administration (FDA) under an emergency use authorization (EUA) for people aged 18 years of age and older. This
6000-575: The Pfizer plant in Puurs was responsible for all vials for destinations outside the United States. Therefore, all doses administered in the Americas outside of the United States before that point in time required at least two transatlantic flights (one to take DNA to Europe and one to bring back finished vaccine vials). In February 2021, BioNTech announced it would increase production by more than 50% to manufacture 2 billion doses in 2021, raised again at
6125-614: The Pfizer-BioNTech vaccine is safe for those with various forms of immunodeficiency or immunosuppression , though it does note that the data on said groups is limited, due to their exclusion from many of the vaccine earlier trials held in 2020. It notes that the World Health Organization advises that the vaccine is among the three COVID-19 vaccines (alongside that of Moderna and AstraZeneca ) it deems safe to give to immunocompromised individuals, and that expert consensus generally recommends their vaccination. The report states that
6250-515: The Pitch study think that the optimal interval against the Delta variant is around eight weeks, with longer intervals leaving receptors vulnerable between doses. A third, fourth, or fifth dose can be added in some countries. A test-negative case-control study published in August 2021, found that two doses of the BNT162b2 (Pfizer) vaccine had 93.7% effectiveness against symptomatic disease caused by
6375-563: The US Centers for Disease Control and Prevention (CDC) between December 2020, and March 2021, on nearly 4 thousand health care personnel, first responders , and other essential and frontline workers concluded that under real-world conditions, mRNA vaccine effectiveness of full immunization (14 days or more after second dose) was 90% against SARS-CoV-2 infections, regardless of symptoms, and vaccine effectiveness of partial immunization (14 days or more after first dose but before second dose)
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#17328760202216500-658: The US CDC confirmed that myocarditis or pericarditis occurs in about 13 of every 1 million young people, mostly male and over the age of 16, who received the Moderna or the Pfizer–BioNTech vaccine . Most affected individuals recover quickly with adequate treatment and rest. Additional side effects include extensive swelling of the vaccinated limb. Moderna's technology uses a nucleoside-modified messenger RNA (modRNA) compound codenamed mRNA-1273. The mRNA-1273 drug delivery system uses
6625-450: The United Kingdom was the first country to authorize its use on an emergency basis. It is authorized for use at some level in the majority of countries. On 23 August 2021, the Pfizer–BioNTech vaccine became the first COVID-19 vaccine to be approved in the US by the Food and Drug Administration (FDA). The logistics of distributing and storing the vaccine present significant challenges due to
6750-498: The United States beginning in fall 2024 should be monovalent JN.1 vaccines. Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments. Multiple steps along the entire development path are evaluated, including: There have been several unique challenges with COVID‑19 vaccine development. Public health programs have been described as "[a] race to vaccinate individuals" with
6875-539: The United States in about 13 per 1 million young people, mostly male and over the age of 16, after vaccination with the Pfizer–BioNTech or the Moderna vaccine . Most affected individuals recover quickly with adequate treatment and rest. Since February 2022, the German Standing Committee on Vaccination recommends aspiration for COVID-19 vaccination as precautionary measure. The BioNTech technology for
7000-454: The adjuvant of choice in some 80% of adjuvanted vaccines. The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including the release of proinflammatory cytokines. In June 2024, the US Food and Drug Administration (FDA) advised the manufacturers of the licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 Formula) for use in
7125-430: The allergic reactions. These vaccines are examples of non-replicating viral vector vaccines using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein. The viral vector-based vaccines against COVID‑19 are non-replicating, meaning that they do not make new virus particles but rather produce only the antigen that elicits a systemic immune response. Authorized vaccines of this type include
7250-469: The alpha (B.1.1.7) variant and 88.0% effectiveness against symptomatic disease caused by the delta (B.1.617.2) variant. Notably, effectiveness after one dose of the Pfizer vaccine was 48.7% against alpha and 30.7% against delta, similar to effectiveness provided by one dose of the ChAdOx1 nCoV-19 vaccine. In August 2021, the US Centers for Disease Control and Prevention (CDC) published a study reporting that
7375-461: The body how to identify and destroy the corresponding pathogen. RNA vaccines often use nucleoside-modified messenger RNA . The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles , which protect the RNA strands and help their absorption into the cells. RNA vaccines are the first COVID‑19 vaccines to be authorized in the United Kingdom, the United States, and
7500-464: The body is building protection to the virus. During clinical trials, the common side effects affecting more than one in 10 people are (in order of frequency): pain and swelling at the injection site, tiredness, headache, muscle aches, chills, joint pain, fever or diarrhea. Fever is more common after the second dose. The European Medicines Agency (EMA) regularly reviews the data on the vaccine's safety. The safety report published on 8 September 2021 by
7625-404: The chronically ill 18–64-year-olds the risk was similar among those who received bivalent vaccine and those who did not. Among the elderly a bivalent booster provided highest protection during the first two months after vaccination, but thereafter signs of waning were observed. The effectiveness among individuals aged 65–79 years and those aged 80 years or more was similar. Based on the results of
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#17328760202217750-562: The desired mRNA strands, which takes about four days. Once the mRNA has been created and purified, it is frozen in plastic bags about the size of a large shopping bag, of which each can hold up to 10 million doses. The bags are placed on trucks which take them to the next plant. The third stage is being conducted at Pfizer plants in Portage, Michigan (near Kalamazoo ) in the United States, and Puurs in Belgium. This stage involves combining
7875-495: The doses purchased by high-income countries comprising 14% of the world's population. Despite the extremely rapid development of effective mRNA and viral vector vaccines , worldwide vaccine equity has not been achieved. The development and use of whole inactivated virus (WIV) and protein-based vaccines have also been recommended, especially for use in developing countries . The 2023 Nobel Prize in Physiology or Medicine
8000-477: The early wave vaccines. Pfizer%E2%80%93BioNTech COVID-19 vaccine ZA : Section 21 The Pfizer–BioNTech COVID-19 vaccine , sold under the brand name Comirnaty , is an mRNA-based COVID-19 vaccine developed by the German biotechnology company BioNTech . For its development, BioNTech collaborated with the American company Pfizer to carry out clinical trials , logistics, and manufacturing. It
8125-417: The effectiveness against infection decreased from 91% ( 81 – 96% ) to 66% ( 26 – 84% ) when the Delta variant became predominant in the US, which may be due to unmeasured and residual confounding related to a decline in vaccine effectiveness over time. Unless indicated otherwise, the following effectiveness ratings are indicative of clinical effectiveness two weeks after the second dose. A vaccine
8250-502: The effectiveness against the Omicron variant starts to decline in about 10 weeks, either after the initial two-dose regimen or after the booster dose. For other variants, the effectiveness of the initial doses starts to decline in about six months. A case-control study in Qatar from 1 January to 5 September 2021 found that effectiveness against infection peaked at 78% (95% CI , 76 – 79% ) in
8375-735: The elderly, and those at high risk of exposure and transmission, such as healthcare workers. Common side effects of COVID‑19 vaccines include soreness, redness, rash, inflammation at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), which resolve without medical treatment within a few days. COVID‑19 vaccination is safe for people who are pregnant or are breastfeeding. As of 12 August 2024 , 13.72 billion doses of COVID‑19 vaccines have been administered worldwide, based on official reports from national public health agencies . By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of
8500-464: The elderly, children, pregnant women , and people with weakened immune systems . Several COVID‑19 vaccines, such as the Pfizer–BioNTech and Moderna vaccines, use RNA to stimulate an immune response. When introduced into human tissue, the vaccine contains either self-replicating RNA or messenger RNA (mRNA), which both cause cells to express the SARS-CoV-2 spike protein . This teaches
8625-414: The end of March to 2.5 billion doses in 2021. In February 2021, Pfizer revealed that the entire sequence initially took about 110 days on average from start to finish, and that the company is making progress on reducing the time to 60 days. More than half the days in the production process are dedicated to rigorous testing and quality assurance at each of the three stages. Pfizer also revealed that
8750-542: The enrollment of 30,000 participants needed for its phase III trial. The US National Institutes of Health announced in November 2020, that overall trial results were positive. Since September 2020, Moderna has used Roche Diagnostics ' Elecsys Anti-SARS-CoV-2 S test, authorized by the US Food and Drug Administration (FDA) under an emergency use authorization (EUA) in November 2020. According to an independent supplier of clinical assays in microbiology, "this will facilitate
8875-521: The face. Documented hypersensitivity to polyethylene glycol (PEG) (a very rare allergy) is listed as a contraindication to the COVID-19 Pfizer vaccine. Severe allergic reaction has been observed in approximately eleven cases per million doses of vaccine administered. According to a report by the US Centers for Disease Control and Prevention , 71% of those allergic reactions happened within 15 minutes of vaccination and mostly (81%) among people with
9000-429: The family Coronaviridae that affect humans have been aimed at severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Vaccines against SARS and MERS have been tested in non-human animals . According to studies published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around
9125-410: The first dose. High efficacy is achieved with full immunization, two weeks after the second dose, and was evaluated at 94.1%: at the end of the vaccine study that led to emergency authorization in the US, there were eleven cases of COVID‑19 in the vaccine group (out of 15,181 people) versus 185 cases in the placebo group (15,170 people). Moreover, there were zero cases of severe COVID‑19 in
9250-400: The first month after the second dose, followed by a slow decline that accelerated after the fourth month, reaching 20% at months 5 to 7. A similar trajectory was observed against symptomatic disease and against specific variants. Effectiveness against severe disease, hospitalization and death was more robust, peaking at 96% ( 93 – 98% ) in the second month and remaining almost stable through
9375-627: The five years it had taken in 1967 when Maurice Hilleman had set the modern record with a vaccine for mumps, followed by the vaccine for Ebola also taking five years. As of 2019 no vaccine existed for preventing a coronavirus infection in humans. The SARS-CoV-2 virus , which causes COVID‑19, was detected in December 2019, The development of the Pfizer- BioNTech COVID‑;19 vaccine began when BioNTech founder and CEO Uğur Şahin while at his home in Mainz on Friday 24 January 2020,
9500-513: The immune system and lessen the severity of COVID‑19 infections. There is experimental evidence that the BCG vaccine for tuberculosis has non-specific effects on the immune system, but there is no evidence that this vaccine is effective against COVID‑19. Most coronavirus vaccines are administered by injection, with further vaccine delivery methods being studied for future coronavirus vaccines. Intranasal vaccines target mucosal immunity in
9625-497: The initial trials used to obtain the emergency use authorization, though trials in those populations were expected to be performed in 2021. In March 2021, in order to increase the span of vaccination beyond adults, Moderna started the clinical trials of vaccines on children age 6-months to 11-years-old in the US and in Canada (KidCove), in addition to the existing and fully-enrolled study on 12-17 year-olds (TeenCOVE). As of December 2020,
9750-530: The issuance of an EUA by the FDA. In February 2021, results from phase III clinical trial were published in the New England Journal of Medicine , indicating 94% efficacy in preventing COVID‑19 infection. Side effects included flu-like symptoms, such as pain at the injection site, fatigue, muscle pain , and headache. The clinical trial is ongoing and is set to conclude in late 2022. Pregnant and breastfeeding women were also excluded from
9875-485: The latest updates. The safety profile of the vaccine is favorable, with common side effects including injection site pain, fatigue, and headaches. Severe reactions like anaphylaxis are exceedingly rare. Concerns regarding myocarditis , have been identified but are typically mild and manageable. The vaccine's formulation utilizes mRNA technology, encapsulated within lipid nanoparticles to ensure cellular uptake and immune system response. The Moderna COVID‑19 vaccine
10000-531: The mRNA with lipid nanoparticles, then filling vials, boxing vials, and freezing them. Croda International subsidiary Avanti Polar Lipids is providing the requisite lipids. As of November 2020, the major bottleneck in the manufacturing process is combining mRNA with lipid nanoparticles. At this stage, it takes only four days to go from mRNA and lipids to finished vials, but each lot must then spend several weeks in deep-freeze storage while undergoing verification against 40 quality-control measures. Before May 2021,
10125-509: The modRNA into the human cells, but also as adjuvants . ALC-0159 is a polyethylene glycol conjugate, i.e., a PEGylated lipid. Pfizer and BioNTech are manufacturing the vaccine in their own facilities in the United States and in Europe. The license to distribute and manufacture the vaccine in China was purchased by Fosun, alongside its investment in BioNTech. Manufacturing the vaccine requires
10250-476: The original amino acids are replaced with prolines , developed by researchers at the University of Texas at Austin and the National Institute of Allergy and Infectious Diseases ' Vaccine Research Center . Once the protein is expelled from the cell, it is eventually detected by the immune system, which begins generating efficacious antibodies. The vaccine contains the following ingredients: The active ingredient
10375-416: The other receiving a placebo of 0.9% sodium chloride. As of 7 August, more than 4,500 volunteers had enrolled. In September 2020, Moderna published the detailed study plan for the clinical trial. In September 2020, CEO Stéphane Bancel said that, if the trial is successful, the vaccine might be available to the public as early as late March or early April 2021. As of October 2020, Moderna had completed
10500-458: The output in 2022, claiming as well that it would make no less than 800 million doses in 2021. The increase in production is in part attributed to improvements made by the company in manufacturing methods. The Moderna news followed preliminary results from the Pfizer - BioNTech vaccine candidate, BNT162b2 , with Moderna demonstrating similar efficacy, but requiring storage at the temperature of
10625-512: The pathogen. The authorized vaccines of this type include the peptide vaccine EpiVacCorona , ZF2001 , MVC-COV1901 , Corbevax , the Sanofi–GSK vaccine , and Soberana 02 (a conjugate vaccine ). Bimervax (selvacovatein) was approved for use as a booster vaccine in the European Union in March 2023. The V451 vaccine was in clinical trials that were terminated after it was found that
10750-441: The phase I dose escalation clinical trial of mRNA-1273, showing dose-dependent induction of neutralizing antibodies against S1/S2 as early as 15 days post-injection. Mild to moderate adverse reactions , such as fever , fatigue, headache, muscle ache , and pain at the injection site were observed in all dose groups, but were common with increased dosage. The vaccine in low doses was deemed safe and effective in order to advance
10875-399: The platforms of vaccine candidates in clinical trials are focused on the coronavirus spike protein (S protein) and its variants as the primary antigen of COVID‑19 infection, since the S protein triggers strong B-cell and T-cell immune responses. However, other coronavirus proteins are also being investigated for vaccine development, like the nucleocapsid , because they also induce
11000-404: The process requires 280 components and relies upon 25 suppliers located in 19 countries. Vaccine manufacturers normally take several years to optimize the process of making a particular vaccine for speed and cost-effectiveness before attempting large-scale production. Due to the urgency presented by the COVID-19 pandemic, Pfizer and BioNTech began production immediately with the process by which
11125-670: The process—synthesis of DNA plasmids (to be used as a template for synthesis of mRNA)—has been handled by a contractor called Aldevron based in Fargo, North Dakota . For the remainder of the process, Moderna contracted with Lonza Group to manufacture the vaccine at facilities in Portsmouth, New Hampshire in the United States, and in Visp in Switzerland, and purchased the necessary lipid excipients from CordenPharma. Besides CMOs, Moderna also manufactures
11250-445: The quantitative measurement of SARS-CoV-2 antibodies and help to establish a correlation between vaccine-induced protection and levels of anti-receptor binding domain (RBD) antibodies." The partnership was announced by Roche on 9 December 2020. A review by the FDA in December 2020, of interim results of the phase III clinical trial on mRNA-1273 showed it to be safe and effective against COVID‑19 infection resulting in
11375-402: The requirement for its storage at extremely low temperatures. In August 2022, a bivalent version of the vaccine (Pfizer-BioNTech COVID-19 Vaccine, Bivalent) was authorized for use as a booster dose in individuals aged twelve and older in the US. The following month, the BA.1 version of the bivalent vaccine (Comirnaty Original/Omicron BA.1 or tozinameran/riltozinameran) was authorized as
11500-593: The restrictions on the Pfizer vaccine were relaxed when the US Food and Drug Administration (FDA) updated the emergency use authorization (EUA) to permit undiluted frozen vials of the vaccine to be transported and stored at between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use. The Moderna vaccine should not be stored at a temperature below −50 °C (−58 °F). In November 2020, Nature reported that "While it's possible that differences in LNP formulations or mRNA secondary structures could account for
11625-652: The results of a preliminary study, the US CDC recommends that pregnant women get vaccinated with the COVID‑19 vaccine. The World Health Organization (WHO) stated that "the safety data supported a favorable safety profile" and that the vaccine's AE ( adverse event ) profile "did not suggest any specific safety concerns". The most common adverse events were pain at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain). The US Centers for Disease Control and Prevention (CDC) has reported anaphylaxis (a severe allergic reaction) in 2.5 cases per million doses administered and has recommended
11750-536: The safety of the Moderna COVID‑19 vaccine during pregnancy. The initial study excluded pregnant women or discontinued them from vaccination upon a positive pregnancy test. Studies in animals found no safety concerns and clinical trials are underway to evaluate the safety and efficacy of COVID‑19 vaccines in pregnant women. Real-world observations through the CDC v-safe tracking program have not uncovered unusual numbers of adverse events or outcomes of interest. Based on
11875-407: The sequence of human alpha globin ; a signal peptide (bases 55–102) and two proline substitutions (K986P and V987P, designated "2P") that cause the spike to adopt a prefusion-stabilized conformation reducing the membrane fusion ability, increasing expression and stimulating neutralizing antibodies; a codon-optimized gene of the full-length spike protein of SARS-CoV-2 (bases 103–3879); followed by
12000-472: The site of injection." The troublesome higher doses were discarded in July from future studies. In September 2021, a study funded by the National Institute of Allergy and Infectious Diseases reported a strong immune response after six months, even at low doses, suggesting that more doses could be deployed from a limited vaccine supply. Six months after low-dose vaccination, 67% of participants still had memory cytotoxic T cells , suggesting that immune memory
12125-421: The sixth month, declining thereafter. In October 2021, a phase III trial showed that a booster dose given approximately 11 months after the second dose restored the protective effect to the 96% (95% CI , 89 – 99% ) efficacy level against symptomatic disease from the Delta variant. In December 2021, Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide
12250-572: The spike proteins were originally developed for a Middle East respiratory syndrome (MERS) vaccine by researchers at the National Institute of Allergy and Infectious Diseases ' Vaccine Research Center , Scripps Research , and Jason McLellan 's team (at the University of Texas at Austin , previously at Dartmouth College ). In addition to the mRNA molecule, the vaccine contains the following inactive ingredients ( excipients ): The first four of these are lipids . The lipids and modRNA together form nanoparticles that act not only as carriers to get
12375-413: The synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an adaptive immune response to the virus before it attaches to a human cell. Vaccine platforms in development may improve flexibility for antigen manipulation and effectiveness for targeting mechanisms of COVID‑19 infection in susceptible population subgroups, such as healthcare workers,
12500-684: The tasks of filling and packaging vials ( fill and finish ), Moderna entered into contracts with Catalent in the United States and Laboratorios Farmacéuticos Rovi in Spain. In April 2021, Moderna expanded its agreement with Catalent to increase manufacturing output at the latter's plant in Bloomington, Indiana . The expansion will allow Catalent to manufacture up to 400 vials per minute and fill an additional 80 million vials per year. Later that month, Moderna announced its plans to spend billions of dollars to boost production of its vaccines, potentially tripling
12625-476: The thermostability differences [between Moderna and BioNtech], many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions." In January 2020, Moderna announced development of an RNA vaccine , codenamed mRNA-1273, to induce immunity to SARS-CoV-2. Moderna received US$ 955 million from the Biomedical Advanced Research and Development Authority (BARDA), an office of
12750-442: The third BioNTech facility in Europe that produces the vaccine, while Pfizer operates at least four production sites in the United States and Europe. The Marburg facility had previously specialized in cancer immunotherapy for Novartis. By the end of March 2021, BioNTech had finished retrofitting the facility for mRNA vaccine production and retraining its 300 staff, and obtained approval to begin manufacturing. Besides making mRNA,
12875-656: The vaccine at its own production facility in Norwood, Massachusetts . Another manufacturing site for the vaccines for the market outside the U.S. (since the end of 2021) is in Geleen in the Netherlands, produced by its manufacturing partner Lonza . Earlier, Lonza did produce the vaccine for the EU, U.K. and Canada at its site in Switzerland only, but had to cut projected deliveries to the U.K. and Canada earlier in 2021 due to production issues. For
13000-672: The vaccine group, versus eleven in the placebo group. This efficacy has been described as "astonishing" and "borderline historic" for a respiratory virus vaccine, and it is similar to the efficacy of the Pfizer–BioNTech COVID-19 vaccine . Efficacy estimates were similar across age groups, sexes, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID‑19. Only individuals aged 18 or older were studied. Studies are underway to gauge efficacy and safety in children aged 0–11 (KidCOVE) and 12–17 (TeenCOVE). A further study conducted by
13125-588: The vaccine had been originally formulated in the laboratory, then started to identify ways to safely speed up and scale up that process. BioNTech announced in September 2020, that it had signed an agreement to acquire a manufacturing facility in Marburg , Germany, from Novartis to expand their vaccine production capacity. Once fully operational, the facility would produce up to 750 million doses per year, or more than 60 million doses per month. The site will be
13250-405: The vaccine in the European Union. The vaccine is delivered in vials that, once diluted, contain 2.25 mL of vaccine, comprising 0.45 mL frozen and 1.8 mL diluent. According to the vial labels, each vial contains five 0.3 mL doses, however excess vaccine may be used for one, or possibly two, additional doses. The use of low dead space syringes to obtain the additional doses
13375-447: The vaccine is out of the question for the world's fourth-most populous country, given that it did not have the necessary cold chain capability. Similarly, India's existing cold chain network can handle only temperatures between 2 and 8 °C (36 and 46 °F), far above the requirements of the vaccine. Before COVID‑19 vaccines, creating a vaccine for an infectious disease from scratch had never before been produced in less than
13500-412: The vaccine is stored in special containers that maintain temperatures between −80 and −60 °C (−112 and −76 °F). Low-income countries have limited cold chain capacity for ultracold transport and storage of a vaccine. The necessary storage temperatures for the vaccine are much lower than for the similar Moderna vaccine . The head of Indonesia 's Bio Farma Honesti Basyir said purchasing
13625-615: The vaccine may potentially cause incorrect results for subsequent HIV testing. The authorized vaccines of this type include the Novavax COVID‑19 vaccine . Additional types of vaccines that are in clinical trials include multiple DNA plasmid vaccines , at least two lentivirus vector vaccines, a conjugate vaccine , and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein. Scientists investigated whether existing vaccines for unrelated conditions could prime
13750-435: The vaccine's high efficacy, with significant effectiveness observed two weeks post-administration of the second dose, offering 94% protection against Covid and robust defense against severe cases. The vaccine's efficacy spans various demographics, including age, sex, and those with high-risk medical conditions. It is an mRNA vaccine composed of nucleoside-modified mRNA (modRNA) encoding a spike protein of SARS-CoV-2, which
13875-625: The vaccines has been found to wane over time, requiring people to get booster doses of the vaccine to maintain protection against COVID‑19. The COVID‑19 vaccines are widely credited for their role in reducing the spread of COVID‑19 and reducing the severity and death caused by COVID‑19. According to a June 2022 study, COVID‑19 vaccines prevented an additional 14.4 to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. Many countries implemented phased distribution plans that prioritized those at highest risk of complications, such as
14000-448: The vaccines were able to generate an immune response in those individuals, though it does also note that this response is weaker than in those that are not immunocompromised. It recommends that specific patient groups, such as those with cancer , inflammatory bowel disease and various liver diseases be prioritised in the vaccination schedules over other patients that do not have said conditions. In September 2021, Pfizer announced that
14125-474: The variant after two doses is about 70% against hospital admission and 33% against symptomatic disease. Protection against hospital admission is maintained for all ages and groups with comorbidities. A study of the bivalent booster effectiveness against severe COVID-19 outcomes in Finland, September 2022–January 2023, has shown that it reduced the risk of severe COVID-19 outcomes among the elderly. By contrast, among
14250-693: The version of the bivalent vaccine used in the United States is based on the Omicron BA.4/BA.5 variant, while the second component of the bivalent vaccine version used in other countries is based on the Omicron BA.1 variant . The vaccine's effectiveness against variants has been extensively studied, indicating varying degrees of protection. For instance, during the prevalence of the Delta variant, effectiveness against infection slightly decreased over time. The vaccine's longevity and continuous protection are under study, with ongoing research focusing on its duration of effectiveness, which remains partially undetermined as of
14375-487: The virus that causes coronavirus disease 2019 ( COVID‑19 ). Before the COVID‑19 pandemic , an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome ( SARS ) and Middle East respiratory syndrome ( MERS ). This knowledge accelerated the development of various vaccine platforms in early 2020. The initial focus of SARS-CoV-2 vaccines
14500-720: The world at that time. There is no cure or protective vaccine proven to be safe and effective against SARS in humans. There is also no proven vaccine against MERS. When MERS became prevalent, it was believed that existing SARS research might provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. As of March 2020, there was one (DNA-based) MERS vaccine that completed Phase I clinical trials in humans, and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA -vectored (MVA-MERS-S). Vaccines that use an inactive or weakened virus that has been grown in eggs typically take more than
14625-497: Was Razi Cov Pars in Iran at the end of October 2021. The first viral component of Sputnik V vaccine was authorised in Russia as Sputnik Nasal in April 2022. In September 2022, India and China approved two nasal COVID‑19 vaccines ( iNCOVACC and Convidecia ), which may (as boosters) also reduce transmission (potentially via sterilizing immunity). In December 2022, China approved
14750-403: Was 80%. The duration of protection provided by the vaccine is unknown as of April 2021, and a two-year followup study is underway to determine the duration. Preliminary results from a phase III trial indicate that vaccine efficacy is durable, remaining at 93% six months after the second dose. A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of
14875-586: Was awarded to Katalin Karikó and Drew Weissman for the development of effective mRNA vaccines against COVID-19. Prior to COVID‑19, a vaccine for an infectious disease had never been produced in less than several years – and no vaccine existed for preventing a coronavirus infection in humans. However, vaccines have been produced against several animal diseases caused by coronaviruses, including (as of 2003) infectious bronchitis virus in birds, canine coronavirus , and feline coronavirus . Previous projects to develop vaccines for viruses in
15000-503: Was checking out his regular websites when he noted a report in the science section of Der Spiegel website about novel respiratory illness that had affected approximately 50 people in Wuhan. He then came across a submission from Hong Kong-based researchers on the website of the medical journal The Lancet in which they discussed a cluster of pneumonia associated with coronavirus and an indication of person-to-person transmission that had affected
15125-501: Was granted to BioNTech Manufacturing GmbH. The EUA amendment for the Pfizer-BioNTech COVID-19 Vaccine (2024-2025 Formula) was issued to Pfizer Inc. The Pfizer–BioNTech COVID-19 vaccine is used to provide protection against COVID-19, caused by infection with the SARS-CoV-2 virus, by eliciting an immune response to the S antigen . The vaccine is used to reduce morbidity and mortality from COVID-19. The vaccine
15250-462: Was on preventing symptomatic, often severe, illness. In 2020, the first COVID‑19 vaccines were developed and made available to the public through emergency authorizations and conditional approvals. Initially, most COVID‑19 vaccines were two-dose vaccines, with the exception single-dose vaccines Convidecia and the Janssen COVID‑19 vaccine , and vaccines with three-dose schedules, Razi Cov Pars and Soberana . However, immunity from
15375-491: Was previously cleared for Ebola. As multiple COVID‑19 vaccines have been authorized or licensed for use, real-world vaccine effectiveness (RWE) is being assessed using case control and observational studies. A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines. As of July 2021, at least nine different technology platforms were under research and development to create an effective vaccine against COVID‑19. Most of
15500-525: Was publicly endorsed by NIAID director Anthony Fauci , virologist Jeffery K. Taubenberger , and David M. Morens. In March 2022, the White House released the "National COVID‑19 Preparedness Plan", which recommended accelerating the development of a universal coronavirus vaccine. One attempt at such a vaccine is being developed at the Walter Reed Army Institute of Research . It uses
15625-510: Was subsequently extended to up to 42 days in the United States, and up to four months in Canada. Clinical trials began in April 2020; by November 2020, the vaccine had entered phase III clinical trials , with over 40,000 people participating. Interim analysis of study data showed a potential efficacy of 91.3% in preventing symptomatic infection within seven days of a second dose and no serious safety concerns. Most side effects are mild to moderate in severity and resolve within
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