Moderna COVID-19 vaccine


The Moderna COVID19 vaccine, sold under the brand name Spikevax among others, is a COVID-19 vaccine developed by the American company Moderna, the United States National Institute of Allergy and Infectious Diseases, and the Biomedical Advanced Research and Development Authority. Depending on the jurisdiction, it is authorized for use in humans aged six months, twelve years, or eighteen years and older. The Moderna COVID19 vaccine provides protection against COVID-19, which is caused by infection by the SARS-CoV-2 virus. In May 2025, a different version of the Moderna COVID-19 vaccine, with the brand name Mnexspike, was approved for medical use in the United States.
Spikevax 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 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.
Spikevax is an mRNA vaccine composed of nucleoside-modified mRNA encoding a spike protein of SARS-CoV-2, which is encapsulated in lipid nanoparticles. In August and September 2022, bivalent versions of the vaccine containing elasomeran/elasomeran 0-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 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 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.

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 into the deltoid muscle of the arm. The initial course consists of two doses. The World Health Organization recommends an interval of eight weeks between doses.
A third, fourth, or fifth dose can be added in some countries.

Efficacy

Evidence of vaccine efficacy 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 versus 185 cases in the placebo group. 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 and 12–17.
A further study conducted by the US Centers for Disease Control and Prevention between December 2020, and March 2021, on nearly 4thousand health care personnel, first responders, and other essential and frontline workers concluded that under real-world conditions, mRNA vaccine effectiveness of full immunization was 90% against SARS-CoV-2 infections, regardless of symptoms, and vaccine effectiveness of partial immunization was 80%.
The duration of protection provided by the vaccine is unknown as of 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.

Effectiveness

A vaccine 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 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 related to a decline in vaccine effectiveness over time.

Specific populations

Limited data are available on the safety of the Moderna COVID19 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 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

The World Health Organization stated that "the safety data supported a favorable safety profile" and that the vaccine's AE profile "did not suggest any specific safety concerns". The most common adverse events were pain at the injection site, fatigue, headache, myalgia, and arthralgia.
The US Centers for Disease Control and Prevention has reported anaphylaxis 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 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.

Pharmacology

Moderna's technology uses a nucleoside-modified messenger RNA compound codenamed mRNA-1273. The mRNA-1273 drug delivery system uses a PEGylated lipid nanoparticle drug delivery 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 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.

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 glycoprotein, with two mutations designed to stabilize the pre-fusion conformation. The sequence is further optimized by:
  • all uridines substituted with N1-methylpseudouridine,
  • flanked by an artificial 5' untranslated region and a 3' UTR derived from the human alpha globin gene,
  • introduction of two additional stop codons,
  • terminated by a 3' poly tail.
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 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 the process—synthesis of DNA plasmids —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 the vaccine at its own production facility in Norwood, Massachusetts. Another manufacturing site for the vaccines for the market outside the U.S. 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 the tasks of filling and packaging vials, 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 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-BioNTech 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 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 updated the emergency use authorization 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 reported that "While it's possible that differences in LNP formulations or mRNA secondary structures could account for the thermostability differences , many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions."