The Moderna COVID19 vaccine (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
: elasomeran), sold under the brand name Spikevax, is a
COVID-19 vaccine
A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID19).
Prior to the COVID19 pandemic, an e ...
developed by American company
Moderna
Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to produ ...
, the United States
National Institute of Allergy and Infectious Diseases (NIAID), and the
Biomedical Advanced Research and Development Authority
The Biomedical Advanced Research and Development Authority (BARDA) is a U.S. Department of Health and Human Services (HHS) office responsible for the procurement and development of medical countermeasures, principally against bioterrorism, in ...
(BARDA). Depending on the jurisdiction, it is authorized for use in people aged six months, twelve years, or eighteen years and older. It provides protection against
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
which is caused by infection by the
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
virus.
It is designed to be administered as two or three 0.5
mL doses given by
intramuscular injection
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
at an interval of at least 28 days apart.
It is an
mRNA vaccine composed of
nucleoside-modified mRNA (modRNA) encoding a
spike protein of SARS-CoV-2, which is encapsulated in
lipid nanoparticles
lipid nanoparticles (LNPs), are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system (and part of nanoparticle drug delivery), and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were f ...
.
It is authorized for use at some level in many countries.
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 years of age or older in the United Kingdom,
Switzerland, Australia, Canada,
the European Union,
and the United States.
The second component of the version of the bivalent vaccine used in the United States (mRNA-1273.222
) is based on the
Omicron BA.4/BA.5 variant,
while the second component in the bivalent vaccine version used in other countries (mRNA-1273.214) is based on the
Omicron BA.1 variant.
Medical uses
The Moderna COVID19 vaccine is used to provide protection against infection by the
SARSCoV2 virus in order to prevent COVID19.
The vaccine is given by
intramuscular injection
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
into the
deltoid muscle of the arm.
The initial course consists of two doses.
The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) recommends an interval of eight weeks between doses.
A third, fourth, or fifth dose can be added in some countries.
Efficacy
![Cumulative incidence curves mRNA-1273](https://upload.wikimedia.org/wikipedia/commons/8/84/Cumulative_incidence_curves_mRNA-1273.jpg)
Evidence of
vaccine efficacy
Vaccine efficacy or vaccine effectiveness is the percentage reduction of disease cases in a vaccinated group of people compared to an unvaccinated group. For example, a vaccine efficacy or effectiveness of 80% indicates an 80% decrease in the ...
starts about two weeks after 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 COVID19 in the vaccine group (out of 15,181 people) versus 185 cases in the
placebo group
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dieta ...
(15,170 people).
Moreover, there were zero cases of severe COVID19 in 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 COVID19.
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 the US
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) between December 2020, and March 2021, on nearly 4thousand health care personnel,
first responder
A first responder is a person with specialized training who is among the first to arrive and provide assistance or incident resolution at the scene of an emergency, such as an accident, disaster, medical emergency, structure fire, crime, or terr ...
s, 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
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
infections, regardless of symptoms, and vaccine effectiveness of partial immunization (14 days or more after first dose but before second dose) was 80%.
[ ]
The duration of protection provided by the vaccine is unknown ,
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.
Effectiveness
A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95%
confidence interval
In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
. Effectiveness is generally expected to slowly decrease over time.
In August 2021, results from a study suggested that the effectiveness against infection decreased from to when the
Delta variant became predominant in the US, which may be due to unmeasured and residual
confounding
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
related to a decline in vaccine effectiveness over time.
Specific populations
Limited data are available on the safety of the Moderna COVID19 vaccine for people who are pregnant.
[ ] 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 COVID19 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 the results of a preliminary study, the US CDC recommends that pregnant women get vaccinated with the COVID19 vaccine.
Adverse effects
![ModernaReaction](https://upload.wikimedia.org/wikipedia/commons/b/b7/ModernaReaction.jpg)
The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(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
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...
(muscle pain), and
arthralgia (joint pain).
The US
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) has reported
anaphylaxis
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...
(a severe allergic reaction) in 2.5 cases per million doses administered and has recommended 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 100mm or greater.
In June 2021, the US CDC confirmed that
myocarditis
Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...
or
pericarditis
Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
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.
Pharmacology
Moderna's technology uses a
nucleoside-modified messenger RNA
A nucleoside-modified messenger RNA (modRNA) is a synthetic messenger RNA (mRNA) in which some nucleosides are replaced by other naturally modified nucleosides or by synthetic nucleoside analogues. modRNA is used to induce the production of a des ...
(modRNA) compound codenamed mRNA-1273. The mRNA-1273 drug delivery system uses a
PEGylated
PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
nanoparticle drug delivery
Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both ...
(LNP) system.
Once the compound is inside a human cell, the mRNA links up with the cell's
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough 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 the original amino acids are replaced with
proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
s, developed by researchers at the
University of Texas at Austin
The University of Texas at Austin (UT Austin, UT, or Texas) is a public research university in Austin, Texas. It was founded in 1883 and is the oldest institution in the University of Texas System. With 40,916 undergraduate students, 11,075 ...
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.
Chemistry
The vaccine contains the following ingredients:
The active ingredient 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:
* all
uridines (U) substituted with
N1-methylpseudouridine (U → m1Ψ),
* flanked by an artificial 5'
untranslated region (UTR) and a 3' UTR derived from the human alpha globin gene (
HBA1),
* introduction of two additional
stop codons,
* terminated by a 3' poly(A) tail.
A putative sequence of the vaccine has been published on a
forum
Forum or The Forum (plural forums or fora) may refer to:
Common uses
* Forum (legal), designated space for public expression in the United States
*Forum (Roman), open public space within a Roman city
**Roman Forum, most famous example
*Internet ...
for professional virologists, obtained by direct sequencing of residual vaccine material in used vials.
The vaccine mRNA is dissolved in an aqueous buffer containing
tromethamine, tromethamine
hydrochloride,
sodium acetate, and
sucrose
Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula .
For human consumption, sucrose is extracted and refined ...
.
The mRNA is encapsulated in
lipid nanoparticle
lipid nanoparticles (LNPs), are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system (and part of nanoparticle drug delivery), and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were f ...
s that stabilize the mRNA and facilitate its entry into cells.
The nanoparticles are manufactured from the following
lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
:
*
1,2-distearoyl-sn-glycero-3-phosphocholine
Distearoylphosphatidylcholine is a phosphatidylcholine, a kind of phospholipid. It is a natural constituent of cell membranes, eg. soybean phosphatidylcholines are mostly different 18-carbon phosphatidylcholines (including minority of saturated DS ...
(DSPC),
*
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
,
*
PEG2000-DMG (polyethylene glycol (PEG) 2000-dimyristoyl glycerol (DMG)),
and
*
SM-102
SM-102 is a synthetic amino lipid which is used in combination with other lipids to form lipid nanoparticles. These are used for the delivery of mRNA-based vaccines, and in particular SM-102 forms part of the drug delivery system for the Moderna ...
Manufacturing
Moderna is relying extensively on
contract manufacturing organization
A contract manufacturing organization (CMO), more recently referred to (and more commonly used now) as a contract development and manufacturing organization (CDMO) to avoid the acronym confusion of Chief Medical Officer or Clinical Monitoring Organ ...
s to scale up its vaccine manufacturing process. The first step of the process—synthesis of DNA
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s (to be used as a template for synthesis of mRNA)—has been handled by a contractor called Aldevron based in
Fargo, North Dakota
Fargo ( /ˈfɑɹɡoʊ/) is a city in and the county seat of Cass County, North Dakota, United States. According to the 2020 census, its population was 125,990, making it the most populous city in the state and the 219th-most populous city in ...
.
For the remainder of the process, Moderna contracted with
Lonza Group
Lonza Group is a Swiss multinational manufacturing company for the pharmaceutical, biotechnology and nutrition sectors, headquartered in Basel, with major facilities in Europe, North America and South Asia. Lonza was established under that name in ...
to manufacture the vaccine at facilities in
Portsmouth, New Hampshire
Portsmouth is a city in Rockingham County, New Hampshire, United States. At the 2020 census it had a population of 21,956. A historic seaport and popular summer tourist destination on the Piscataqua River bordering the state of Maine, Portsmou ...
in the United States, and in
Visp in Switzerland, and purchased the necessary lipid
excipients from CordenPharma.
Besides CMOs, Moderna also manufactures the vaccine at its own production facility in
Norwood, Massachusetts
Norwood is a town and census-designated place in Norfolk County, Massachusetts, United States. Norwood is part of the Greater Boston area. As of the 2020 census, the population was 31,611. The town was named after Norwood, England. Norwood is ...
.
For the tasks of filling and packaging vials (
fill and finish
In the pharmaceutical industry, fill and finish (also referred to as fill finish, fill-finish or fill/finish) is the process of filling vials with vaccine , biological and pharmaceutical Drug Substances (DS) and finishing the process of packaging t ...
), 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
Bloomington is a city in and the county seat of Monroe County, Indiana, Monroe County in the central region of the U.S. state of Indiana. It is the List of municipalities in Indiana, seventh-largest city in Indiana and the fourth-largest outside ...
. The expansion will allow Catalent to manufacture up to 400 vials per minute and fill an additional 80million vials per year. Later that month, Moderna announced its plans to spend billions of dollars to boost production of its vaccines, potentially tripling the output in 2022, claiming as well that it would make no less than 800million 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
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
-
BioNTech
BioNTech SE ( ; or short for Biopharmaceutical New Technologies) is a German biotechnology company based in Mainz that develops and manufactures active immunotherapies for patient-specific approaches to the treatment of diseases. It develops ...
vaccine candidate,
BNT162b2, with Moderna demonstrating similar efficacy, but requiring storage at the temperature of a standard medical refrigerator of for up to thirty days or for up to four months, whereas the Pfizer-BioNTech candidate requires
ultracold freezer
An ultra low temperature (ULT) freezer is a refrigerator that stores contents at between . An ultra low temperature freezer is commonly referred to as a "minus 80 freezer" or a "negative 80 freezer", referring to the most common temperature standa ...
storage between .
[ Low-income countries usually have cold chain capacity for only standard refrigerator storage, not ultracold freezer storage. In February 2021, the restrictions on the Pfizer vaccine were relaxed when the US ]Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) updated the emergency use authorization (EUA) to permit undiluted frozen vials of the vaccine to be transported and stored at between for up to two weeks before use. The Moderna vaccine should not be stored at a temperature below .
In November 2020, ''Nature
Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...
'' reported that "While it's possible that differences in LNP formulations or mRNA secondary structures could account for the thermostability differences etween Moderna and BioNtech many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions."
History
Original version
In January 2020, Moderna announced development of an RNA vaccine, codenamed mRNA-1273, to induce immunity to SARS-CoV-2.
Moderna received from the Biomedical Advanced Research and Development Authority
The Biomedical Advanced Research and Development Authority (BARDA) is a U.S. Department of Health and Human Services (HHS) office responsible for the procurement and development of medical countermeasures, principally against bioterrorism, in ...
(BARDA), an office of 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 $2.5billion in total funding for the Moderna COVID19 vaccine (mRNA-1273). Private donors also made contributions to the vaccine's development. The Dolly Parton
Dolly Rebecca Parton (born January 19, 1946) is an American singer-songwriter, actress, philanthropist, and businesswoman, known primarily for her work in country music. After achieving success as a songwriter for others, Parton made her album d ...
COVID-19 Research Fund contributed $1million.
Phase I–II clinical trials
In March 2020, the phaseI 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
The Biomedical Advanced Research and Development Authority (BARDA) is a U.S. Department of Health and Human Services (HHS) office responsible for the procurement and development of medical countermeasures, principally against bioterrorism, in ...
(BARDA) allocated up to $483million for Moderna's vaccine development. Plans for a phaseII dosing and efficacy trial to begin in May were approved by the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA). Moderna signed a partnership with Swiss vaccine manufacturer Lonza Group
Lonza Group is a Swiss multinational manufacturing company for the pharmaceutical, biotechnology and nutrition sectors, headquartered in Basel, with major facilities in Europe, North America and South Asia. Lonza was established under that name in ...
, to supply 300million doses per annum.
On 25 May 2020, Moderna began a phaseIIa clinical trial recruiting six hundred adult participants to assess safety and differences in antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
response to two doses of its candidate vaccine, mRNA-1273, a study expected to complete in 2021.
On 14 July 2020, Moderna scientists published preliminary results of the phaseI 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 reaction
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s, such as fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, 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 a phaseIII clinical trial using two 100-μg doses administered 29 days apart.[
On 14 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
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
cytotoxic T cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
s, suggesting that immune memory 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.
Phase III clinical trials
Moderna and the National Institute of Allergy and Infectious Diseases began a phaseIII trial in the US on 27 July, with a plan to enroll and assign thirty-thousand volunteers to two groupsone group receiving two 100-μg doses of mRNA-1273 vaccine and the other receiving a placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
of 0.9% sodium chloride. As of 7August, more than 4,500 volunteers had enrolled.
In September 2020, Moderna published the detailed study plan for the clinical trial. On 30 September, 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 the enrollment of 30,000 participants needed for its phaseIII trial. The US National Institutes of Health announced on 15 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
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) under an emergency use authorization (EUA) on 25 November 2020. According to an independent supplier of clinical assays in microbiology, "this will facilitate 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 9December 2020.
A review by the FDA in December 2020, of interim results of the phaseIII clinical trial on mRNA-1273 showed it to be safe and effective against COVID19 infection resulting in the issuance of an EUA by the FDA.[
In February 2021, results from phaseIII clinical trial were published in '']the New England Journal of Medicine
''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one.
His ...
'', indicating 94% efficacy in preventing COVID19 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 the initial trials used to obtain the emergency use authorization, though trials in those populations were expected to be performed in 2021.
On 16 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).
Authorizations
= Expedited
=
As of December 2020, the Moderna COVID19 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.
On 18 December 2020, the Moderna COVID19 vaccine was authorized by the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) under an emergency use authorization (EUA) for people aged 18 years of age and older.[ ] This 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.
On 23 December 2020, the Moderna COVID19 vaccine was authorized by Health Canada
Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary unit ...
.
On 5 January 2021, the Moderna COVID19 vaccine was authorized for use in Israel by its Ministry of Health.
On 3 February 2021, the Moderna COVID19 vaccine was authorized for use in Singapore by its Health Sciences Authority
The Health Sciences Authority (HSA) is a statutory board under the Ministry of Health of the Government of Singapore. It is a multi-disciplinary agency, responsible for applying medical, pharmaceutical and scientific expertise to protect and ...
.
On 30 April 2021, the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) granted emergency use listing.
On 5 May 2021, the Moderna COVID19 vaccine was authorized for emergency use in the Philippines by the Philippines Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
.
In 2020, Moderna partnered with Takeda Pharmaceutical Company, and the Japan Ministry of Health, Labour and Welfare (MHLW). The vaccine is known as "COVID-19 Vaccine Moderna Intramuscular Injection". On 21 May 2021, COVID19 Vaccine Moderna Intramuscular Injection (formerly TAK-919) was authorized for emergency use in Japan.
On 29 June 2021, the Moderna COVID19 vaccine was authorized for use in India by the Drugs Controller General of India
Drugs Controller General of India (DCGI) is the head of department of the Central Drugs Standard Control Organization of the Government of India responsible for approval of licences of specified categories of drugs such as blood and blood p ...
. The same day, the vaccine was also approved by the Ministry of Health of Vietnam for emergency use in the country.
On 5 August 2021, Malaysia's National Pharmaceutical Regulatory Agency (NPRA) gave conditional registration for emergency use of the Moderna COVID19 vaccine.
= Standard
=
On 6 January 2021, the Committee for Medicinal Products for Human Use
The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...
(CHMP) of the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) recommended granting conditional marketing authorization and the recommendation was accepted by the European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
the same day. On 23 July 2021, the EMA extended the use of the COVID19 Vaccine Moderna to include people aged 12 to 17.
On 12 January 2021, Swissmedic
The Swiss Agency for Therapeutic Products (Swissmedic) is the Swiss surveillance authority for medicines and medical devices, registered in Bern. It began operations on 1 January 2002 as successor of ''Interkantonale Kontrollstelle für Heilmittel ...
granted temporary authorization for the Moderna COVID-19 mRNA Vaccine in Switzerland.
On 31 March 2021, the Medicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably ...
(MHRA) granted conditional marketing authorization in the United Kingdom.
On 9 August 2021, Spikevax was granted provisional approval in Australia. The approval was updated on 4 September 2021, to include people aged twelve and older.
The Moderna Spikevax COVID-19 vaccine was authorized in Canada on 16 September 2021, for people aged 12 and older.
The Moderna Spikevax COVID-19 vaccine was authorized in the US on 31 January 2022, for people aged 18 and older.
The Moderna Spikevax Bivalent Zero/Omicron vaccine was approved for medical use in the United Kingdom in August 2022.
In September 2022, the CHMP of the EMA recommended converting the conditional marketing authorizations of the vaccine into standard marketing authorizations.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] The recommendation covers all existing and upcoming adapted Spikevax vaccines, including the recently-approved adapted Spikevax bivalent Original/Omicron BA.1.
Boosters
In January 2021, Moderna announced that it would offer a third dose of its vaccine to people who were vaccinated twice in its phaseI trial. The booster would be made available to participants six to twelve months after they got their second dose. The company said it may also study a third shot in participants from its phaseIII trial, if antibody persistence data warranted it. It also started testing to see if a third shot of the existing vaccine could be used to fend off the virus variants.
In August 2021, the US Food and Drug Administration (FDA) and the US Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) authorized the use of an additional mRNA vaccine dose for immunocompromised individuals.[ ]
In September 2021, the Committee for Medicinal Products for Human Use
The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...
(CHMP) of the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) started evaluating the use of a booster dose of the Moderna COVID-19 vaccine to be given at least six months after the second dose in people aged twelve years and older.
On 4 October 2021, the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
(EMA) stated that people with "severely weakened" immune systems can receive an extra dose of either the Pfizer–BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine starting at least 28 days after their second dose.
In October 2021, the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) and the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) authorized the use of either homologous or heterologous vaccine booster doses.[ ][ ][ ] The authorization was expanded to include all adults in November 2021.
Variants
In January 2021, Moderna started development of a new form of its vaccine, called mRNA-1273.351, that could be used as a booster shot against the Beta variant
The Beta variant, (B.1.351), was a variant of SARS-CoV-2, the virus that causes COVID-19. One of several SARS-CoV-2 variants initially believed to be of particular importance, it was first detected in the Nelson Mandela Bay metropolitan are ...
(lineage B.1.351). On 24 February, Moderna announced that it had manufactured and shipped sufficient amounts of mRNA-1273.351 to the National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
to run phaseI clinical trials. Moderna also investigated a multivalent booster, mRNA-1273.211, which combines a 50-50 mix of mRNA-1273 and mRNA-1273.351.
A bivalent version of the vaccine containing elasomeran/imelasomeran (Spikevax bivalent Original/Omicron) was approved for use in the United Kingdom and in Australia in August 2022. It was approved for use in Canada in September 2022.
In October 2022, the FDA amended the authorization for the bivalent booster to cover people aged six years of age and older.[ ]
Society and culture
About 155million doses of the Moderna COVID-19 vaccine, including about 3.1million doses in children and adolescents (below 18 years of age) were administered in the EU/ EEA from authorization to 26 June 2022.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
Brand names
mRNA-1273 was the code name during development and testing, elasomeran is the international nonproprietary name (INN), and Spikevax is the brand name.
Economics
In June 2020, Singapore
Singapore (), officially the Republic of Singapore, is a sovereign island country and city-state in maritime Southeast Asia. It lies about one degree of latitude () north of the equator, off the southern tip of the Malay Peninsula, borde ...
signed a pre-purchase agreement for Moderna, reportedly paying a price premium in order to secure early stock of vaccines, although the government declined to provide the actual price and quantity, citing commercial sensitivities and confidentiality clauses.
On 11 August 2020, the US government signed an agreement to buy 100million doses of Moderna's anticipated vaccine, which the ''Financial Times
The ''Financial Times'' (''FT'') is a British daily newspaper printed in broadsheet and published digitally that focuses on business and economic current affairs. Based in London, England, the paper is owned by a Japanese holding company, Nik ...
'' said Moderna planned to price at per course. In November 2020, Moderna said it will charge governments who purchase its vaccine between and per dose while the EU is seeking a price of under per dose for the 160million doses it plans to purchase from Moderna.
In 2020, Moderna obtained purchase agreements for mRNA-1273 with the European Union for 160million doses and with Canada for up to 56million doses. On 17 December, a tweet by the Belgium Budget State Secretary revealed the E.U. would pay per dose, while ''The New York Times
''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...
'' reported that the US would pay per dose.
Moderna reported revenue of from its COVID19 vaccine in 2020, and $17.7billion in 2021.
Paused vaccinations
Out of concern that the vaccine may increase the risk of myocarditis
Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...
in young people under age 30, Finland, Sweden, Germany, and France recommended Moderna vaccinations not be used for this age group in October/November 2021.
Controversies
In May 2020, after releasing partial and non-peer reviewed results for only eight of 45 candidates in a preliminary pre-phaseI stage human trial directly to financial markets, the CEO announced on CNBC
CNBC (formerly Consumer News and Business Channel) is an American basic cable business news channel. It provides business news programming on weekdays from 5:00 a.m. to 7:00 p.m., Eastern Time, while broadcasting talk sho ...
an immediate $1.25billion rights issue to raise funds for the company, at a $30billion valuation, while ''Stat
STAT, Stat. , or stat may refer to:
* Stat (system call), a Unix system call that returns file attributes of an inode
* ''Stat'' (TV series), an American sitcom that aired in 1991
* Stat (website), a health-oriented news website
* STAT protein, a ...
'' said, "Vaccine experts say Moderna didn't produce data critical to assessing COVID19 vaccine."
On 7 July 2020, disputes between Moderna and government scientists over the company's unwillingness to share data from the clinical trials were revealed.
Moderna also faced criticism for failing to recruit people of color in clinical trials.
On 18 August 2021, the US Department of Health and Human Services announced a plan to offer a booster dose
A booster dose is an extra administration of a vaccine after an earlier (primer) dose. After initial immunization, a booster provides a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to protec ...
eight months after the second dose, citing evidence of reduced protection against mild and moderate disease and the possibility of reduced protection against severe disease, hospitalization, and death. Scientists and the WHO reaffirmed the lack of evidence on the need for a booster dose for healthy people and that the vaccine remains effective against severe disease months after administration. In a statement, the WHO and SAGE
Sage or SAGE may refer to:
Plants
* ''Salvia officinalis'', common sage, a small evergreen subshrub used as a culinary herb
** Lamiaceae, a family of flowering plants commonly known as the mint or deadnettle or sage family
** ''Salvia'', a large ...
said that, while protection against infection may be diminished, protection against severe disease will likely be retained due to cell-mediated immunity
Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
. Research into optimal timing for boosters is still ongoing, and a booster too early may lead to less robust protection.
Misinformation
Videos on video-sharing platforms circulated around May 2021 showing people having magnets stick to their arms after receiving the vaccine, purportedly demonstrating the conspiracy theory that vaccines contain microchips, but these videos have been debunked.
In November 2021, a White House correspondent for the conservative outlet Newsmax
Newsmax (Newsmax Media, Inc. or Newsmax.com, previously styled NewsMax) is an American right-wing to far-right cable news and digital media company founded by Christopher Ruddy on September 16, 1998. Newsmax Media divisions include its cable ...
falsely tweeted that the Moderna vaccine contained luciferase
Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words ''luciferin'' and ''luciferase'', ...
"so that you can be tracked."
Patent litigation
The PEGylated
PEGylation (or pegylation) is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol (PEG, in pharmacy called macrogol) polymer chains to molecules and macrostructures, such as a drug, therapeutic protein ...
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
nanoparticle (LNP) drug delivery system of mRNA-1273 has been the subject of ongoing patent litigation with Arbutus Biopharma
Arbutus Biopharma Corporation is a publicly traded Canadian (NASDAQ: ABUS) biopharmaceutical company with an expertise in liposomal drug delivery and RNA interference, and is developing drugs for hepatitis B infection.
It is headquartered in Va ...
, from whom Moderna had previously licensed LNP technology. On 4September 2020, '' Nature Biotechnology'' reported that Moderna had lost a key challenge in the ongoing case.
Explanatory notes
References
Further reading
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External links
Entry in the Drug Information Portal
of the U.S. National Library of Medicine.
from the US Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
Safety Updates
from the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
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