Spikevax (Original) was proven effective in adults starting 14 days after dose 2 of primary series2*
COVE study results*: proven protection confirmed by RT-PCR.2,4
Severe cases of COVID-19 were defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition plus any of the following2‡:
Clinical signs indicative of severe systemic illness, respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic BP <90 mm Hg, diastolic BP <60 mm Hg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death.
Primary endpoint subgroup analyses4
93.4%
effective against COVID-19† at 4 months in adults aged 18-64 years studied2
(n=10,661)
Primary endpoint subgroup analyses4
91.5%
effective against COVID-19† at 4 months in adults aged ≥65 years studied2
(n=3626)
Secondary endpoint4
98.2%
effective in preventing severe cases of COVID-19 in adults aged ≥18 years studied2
(n=14,287)
Superior immunogenicity demonstrated with the bivalent booster in vaccinated adults aged 18 years and older2
GMT ratio2
6.3x
(5.3, 7.5; 95% CI)
the immune response in participants (n=209) who received a second booster dose of Moderna COVID-19 Vaccine, Bivalent (Original, BA.4/BA.5) vs participants (n=259) who received a second booster dose of Spikevax (Original)2
The GMT was 2747.3 (2399.2, 3145.9; 95% CI) for participants (n=209) who received the bivalent booster (Original, BA.4/BA.5) vs 436.7 (389.1, 490.0; 95% CI) for participants (n=259) who received Spikevax (Original)2
The bivalent booster demonstrated superior immune response satisfying the criteria for success.2 Superiority is declared if the lower limit of the 2-sided 95% CI for the GMT ratio is >1.
Seroresponse results: The rate difference was 53.9. Seroresponse was 90.9 (86.2, 94.4; 95% CI) for participants (n=209) who received the bivalent booster (Original, BA.4/BA.5) vs 37.8 (31.9, 44.0; 95% CI) for participants (n=259) who received Spikevax (Original).2
The success criteria were met.2
Immune response of Moderna COVID-19 Vaccine, Bivalent was studied in infants and children2
Effectiveness of a single dose of Moderna COVID-19 Vaccine, Bivalent booster given 29 days post-dose was proven in 2 studies. Study 3 compared immune response, in participants aged 12–17 years vs 18–25 years, who received Spikevax (Original). Study 6 compared immune response in participants aged 6 months–5 years who were given a bivalent booster vs those who completed the Spikevax (Original) primary series only.2
Participants aged 12-17 years vs 18-25 years (Study 3)
GMC ratio2
49.0x
(44.2, 54.2; 95% CI)
the immune response in participants aged 12–17 years (n=245) vs 18–25 years (n=294).
The GMC was 2771.0 (2570.0, 2987.6; 95% CI) for participants (n=245) aged 12–17 years who received the bivalent booster (Original and BA.5/BA.5) vs 56.6 (52.8, 60.6; 95% CI) for adults (n=294) aged 18–25 years who received Spikevax (Original).2
The Moderna COVID-19 Vaccine, Bivalent booster (Original and BA.5/BA.5) demonstrated superior immune response satisfying the success criteria.2 The superiority of GMC against Omicron BA.4/BA.5 is demonstrated if the lower limit of the 2-sided 95% CI for the GMC ratio is >1.
Participants aged 6 months–5 years (Study 6)
GMC ratio2
12.1x
(10.7, 13.6; 95% CI)
the immune response in participants (n=316) who received the bivalent booster (Original and BA.1) vs participants (n=567) who received Spikevax (Original).
The GMC was 805.2 (731.2, 886.8; 95% CI) for participants (n=316) who received the Moderna COVID-19 Vaccine, Bivalent booster (Original and BA.1) vs 66.6 (62.0, 71.6; 95% CI) for participants (n=567) who received Spikevax (Original).2
The Moderna COVID-19 Vaccine, Bivalent booster (Original and BA.1) demonstrated the superior immune response satisfying the success criteria.2 The superiority of GMC against Omicron BA.1 is demonstrated if the lower limit of the 2-sided 95% CI for the GMC ratio is >1.
Seroresponse results: The rate difference was 14.2 (11.1, 17.5; 95% CI). Seroresponse was 99.0 (97.2, 99.8; 95% CI) for participants (n=312) who received the bivalent booster (Original and BA.1) vs 84.9 (81.6, 87.7; 95% CI) participants (n=562) who received Spikevax (Original).2
The success criteria were met.2
Spikevax safety from clinical studies2
Most commonly reported (≥10%) adverse reactions following administration of Spikevax (Original) or Moderna COVID-19 Vaccine, Bivalent containing the same amount of mRNA as the Spikevax 2025-2026 Formula:
Adverse reactions | 6 months–36 months of age |
|---|---|
| Irritability/crying | up to 82.8% |
| Pain at the injection site | up to 77.2% |
| Sleepiness | up to 52.2% |
| Loss of appetite | up to 46.5% |
| Fever | up to 26.8% |
| Erythema | up to 19.2% |
| Swelling at the injection site | up to 19.2% |
| Axillary (or groin) swelling/tenderness | up to 12.2% |
Adverse reactions | 37 months–11 years of age |
|---|---|
| Pain at the injection site | up to 98.4% |
| Fatigue | up to 73.2% |
| Headache | up to 62.2% |
| Myalgia | up to 35.3% |
| Chills | up to 34.6% |
| Nausea/vomiting | up to 29.3% |
| Axillary (or groin) swelling/tenderness | up to 27.0% |
| Fever | up to 25.8% |
| Erythema | up to 24.1% |
| Swelling at the injection site | up to 22.3% |
| Arthralgia | up to 21.3% |
Adverse reactions | 12–17 years of age |
|---|---|
| Pain at the injection site | up to 90.6% |
| Fatigue | up to 58.1% |
| Headache | up to 56.3% |
| Myalgia | up to 40.1% |
| Chills | up to 30.2% |
| Axillary swelling/tenderness | up to 27.8% |
| Arthralgia | up to 23.9% |
| Nausea/vomiting | up to 17.9% |
| Swelling at the injection site | up to 13.3% |
Adverse reactions | 18-64 years of age |
|---|---|
| Pain at the injection site | up to 86.3% |
| Fatigue | up to 62.0% |
| Headache | up to 58.9% |
| Myalgia | up to 49.6% |
| Arthralgia | up to 41.9% |
| Chills | up to 40.3% |
| Axillary swelling/tenderness | up to 24.8% |
| Nausea/vomiting | up to 16.7% |
Adverse reactions | 65 years and older |
|---|---|
| Pain at the injection site | up to 76.3% |
| Fatigue | up to 58.1% |
| Myalgia | up to 47.4% |
| Headache | up to 42.1% |
| Arthralgia | up to 39.5% |
| Chills | up to 18.4% |
| Axillary swelling/tenderness | up to 14.3% |
Spikevax clinical study designs
Study | COVE2,4 | Bivalent2,5 |
|---|---|---|
Objective | 1:1 randomized, stratified, observer-blind, placebo-controlled study, comparing Spikevax (Original) primary series (mRNA 100 mcg per dose) vs placebo | Open-label, phase 2/3 study, comparing Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) booster (mRNA 50 mcg per dose) vs Spikevax (Original) booster (mRNA 50 mcg per dose) |
Subjects | 30,346 adults aged ≥18 years | 819 adults aged ≥18 years† |
Primary endpoints | Safety and efficacy of Spikevax in preventing COVID-19 (confirmed by a RT-PCR test) Reactogenicity of 2 injections of Spikevax given 1 month apart | Safety and reactogenicity of Moderna COVID-19 Vaccine, Bivalent and Spikevax (Original) |
Secondary endpoints | Prevention of severe COVID-19* | Noninferiority (on the basis of the difference in the percentage of participants with a seroresponse) against ancestral SARS-CoV-2 28 days after the second booster |
Study | Study 32 | Study 62 |
|---|---|---|
Objective | The study was conducted in multiple parts. • Phase 3, randomized (2:1), placebo-controlled, observer-blind • Open-label booster study | • Phase 3, ongoing open-label booster study |
Subjects | • 3,733 participants aged 12–17 years • 539 participants aged 12–17 years in the open-label booster study | • 909 participants aged 6 months–5 years |
Primary endpoints | • Safety, reactogenicity, and effectiveness of SPIKEVAX (Original) vaccine (mRNA 100 mcg per dose) • Open-label booster study evaluated the immunogenicity of Moderna COVID-19 Vaccine (Original and BA.4/BA.5) (mRNA 10 mcg per dose) compared to Spikevax (Original, Monovalent) vaccine (mRNA 100 mcg per dose) | • Immunogenicity of Moderna COVID-19 Vaccine (Original, BA.1) (mRNA 10 mcg per dose) compared to Spikevax (Original, Monovalent) vaccine (mRNA 25 mcg per dose) as measured by GMC ratio and difference in seroresponse rates |
Secondary endpoints | • Seroresponse in the open-label extension study |
*Median length of follow-up was 4 months. Data analysis prior to the emergence of the Delta and Omicron variants.
†Effectiveness is defined as preventing COVID-19, which was defined according to the following criteria: The participant must have experienced ≥2 of the following systemic symptoms: fever (≥38 °C/≥100.4 °F), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s); or the participant must have experienced ≥1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographic evidence of pneumonia; and the participant must have ≥1 NP swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR.
‡Severe cases of COVID-19 were defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition plus any 1 other item.
ARDS = acute respiratory distress syndrome
BP = blood pressure
COVID-19 = coronavirus disease 2019
ECMO = extracorporeal membrane oxygenation
FIO2 = fraction of inspired oxygen
GMC = geometric mean concentration
GMT = geometric mean titer
NP = nasopharyngeal
PaO2 = partial pressure of oxygen; RT-PCR, reverse transcription polymerase chain reaction
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2
SpO2 = oxygen saturation
Study design footnotes*Severe cases of COVID-19 were defined based on confirmed COVID-19 as per the primary efficacy endpoint case definition, plus any of the following: Clinical signs indicative of severe systemic illness, respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or PaO2/FIO2 <300 mm Hg; or respiratory failure or ARDS (defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO), evidence of shock (systolic BP <90 mm Hg, diastolic BP <60 mm Hg or requiring vasopressors); or significant acute renal, hepatic, or neurologic dysfunction; or admission to an intensive care unit or death.
†Subjects had previously received two 100-mcg doses of the Spikevax (Original) primary series and one 50-mcg dose Spikevax (Original) primary series booster ≥3 months before enrollment.
See above for abbreviationsINDICATION
SPIKEVAX® (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
SPIKEVAX is approved for use in individuals who are:
- 65 years of age and older, or
- 6 months through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19.
IMPORTANT SAFETY INFORMATION
Contraindications
Do not administer SPIKEVAX® to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of SPIKEVAX or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Moderna COVID-19 vaccine.
Warnings and Precautions
- Management of Acute Allergic Reactions: Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of SPIKEVAX.
- Myocarditis and Pericarditis: Postmarketing data with authorized or approved mRNA COVID-19 vaccines have demonstrated increased risks of myocarditis and pericarditis, with onset of symptoms typically in the first week following vaccination. The observed risk has been highest in males 12 years through 24 years of age.
- Syncope (fainting): May occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
- Altered Immunocompetence: Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished immune response to SPIKEVAX.
- Limitations of Vaccine Effectiveness: SPIKEVAX may not protect all vaccine recipients.
Adverse Reactions
The most commonly reported (>10%) adverse reactions in participants 6 - 36 months of age: irritability/crying, pain at the injection site, sleepiness, loss of appetite, fever, erythema, swelling at the injection site, and axillary (or groin) swelling/tenderness.
The most commonly reported (>10%) adverse reactions in participants 37 months - 11 years of age were: pain at the injection site, fatigue, headache, myalgia, chills, nausea/vomiting, axillary (or groin) swelling/tenderness, fever, erythema, swelling at the injection site, and arthralgia.
The most commonly reported (≥10%) adverse reactions in participants 12 years and older were: pain at the injection site, headache, fatigue, myalgia, arthralgia, chills, and axillary swelling/tenderness, nausea/vomiting, and swelling at the injection site.
Reporting Adverse Events and Vaccine Administration Errors
To report suspected adverse reactions, contact ModernaTX, Inc. at 1-866-663-3762 or VAERS at 1-800-822-7967 or https://vaers.hhs.gov.
Please click for Full Prescribing Information.
References
- Centers for Disease Control. About COVID-19. Updated June 13, 2024. Accessed July 25, 2025. https://www.cdc.gov/covid/about/index.html
- Spikevax. Prescribing Information. ModernaTX, Inc.
- Food and Drug Administration. COVID-19 vaccines (2025-2026 Formula) for use in the United States beginning in fall 2025. Updated May 22, 2025. Accessed August 7, 2025. https://www.fda.gov/vaccines-blood-biologics/industry-biologics/covid-19-vaccines-2025-2026-formula-use-united-states-beginning-fall-2025
- Baden LR, El Sahly HM, Essink B, et al. COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi: 101056/NEJMoa2035389
- Chalkias S, Harper C, Vrbicky K, et al. A bivalent omicron-containing booster vaccine against Covid-19. N Engl J Med. 2022387(14):1279-1291. doi: 10.1056/NEJMoa2208343
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