Monkeypox is a potentially serious disease caused by infection with the monkeypox virus, a zoonotic orthopoxvirus closely related to smallpox1 2. Vaccination remains a key strategy to prevent monkeypox infection and reduce disease severity, especially in at-risk populations3 4. Two vaccines are currently approved in the United States for monkeypox prevention: JYNNEOS and ACAM2000, with JYNNEOS being preferred due to its improved safety profile and non-replicating nature5 6. Understanding the side effects and dosing options of these vaccines helps optimize protection while managing adverse reactions effectively7 8.
“The most common vaccine side effects are pain, redness, swelling, hardness, itching at the injection site.”
— Elsbet Servay, Callen-Lorde Community Health Center8
Monkeypox Vaccines for At-Risk Groups
Two vaccines are authorized by the FDA to prevent monkeypox: JYNNEOS and ACAM20005 6. JYNNEOS is a live, non-replicating Modified Vaccinia Ankara (MVA) vaccine, while ACAM2000 is a live, replication-competent vaccinia virus vaccine9 10. The non-replicating nature of JYNNEOS means it does not produce infectious virus in humans and cannot cause clinical vaccinia infections, making it safer for widespread use1 . In contrast, ACAM2000 can cause clinical vaccinia infections and shed live virus from the vaccination site, posing transmission risks to close contacts11 5.
JYNNEOS is administered as a two-dose series, with doses given 28 days apart7 3. Full protection develops approximately two weeks after the second dose8 . The vaccine can be given either subcutaneously or intradermally; the latter route has been authorized under emergency use to extend vaccine supply by using a smaller volume per dose while maintaining effectiveness7 12. ACAM2000 is given as a single dose via percutaneous scarification but is contraindicated in immunocompromised individuals and those with certain skin conditions due to higher risks of serious side effects11 13.
The Centers for Disease Control and Prevention (CDC) recommends JYNNEOS as the primary vaccine for monkeypox prevention because of its better safety profile and ease of administration1 3. Vaccination is advised for people with known or suspected exposure to monkeypox, men who have sex with men and transgender or nonbinary individuals with certain risk factors, those with recent sexual partners diagnosed with monkeypox, and persons at occupational risk for orthopoxvirus exposure3 .
| Vaccine | Type | Dose Schedule | Key Risks/Side Effects | Administration Route |
|---|---|---|---|---|
| JYNNEOS | Live, non-replicating | 2 doses, 28 days apart | Injection site reactions, mild systemic symptoms | Subcutaneous or intradermal |
| ACAM2000 | Live, replicating | Single dose | Myocarditis, pericarditis, transmission risk | Percutaneous scarification |
“One time I bumped the back of my arm on something and it hurt a LOT for a few seconds, like a stubbed toe.”
— Graham Walker, San Francisco ER8
Common Monkeypox Vaccine Side Effects
Side effects from monkeypox vaccines are generally uncommon and mostly mild, with serious adverse events being very rare10 24. The most frequently reported side effects of the JYNNEOS vaccine are local reactions at the injection site, including pain, redness, swelling, hardness, and itching17 2526. These local reactions may be more pronounced with intradermal injections compared to subcutaneous shots, often resulting in a bump or hard lump that can linger for days or weeks17 8. Systemic symptoms such as headache, fatigue, muscle aches (myalgia), chills, fever, and nausea have also been observed following JYNNEOS vaccination22 2726.
Severe allergic reactions to JYNNEOS are rare but can include anaphylaxis symptoms such as swelling and respiratory difficulty, which require immediate medical attention21 22. Importantly, data from clinical trials involving nearly 8,000 participants, including those with HIV or other immunocompromising conditions, showed a favorable safety profile for JYNNEOS without increased risk of myocarditis or pericarditis compared with placebo controls1 .
In contrast, ACAM2000 has a higher risk of serious side effects. Common side effects include rash, fever, fatigue, itching, swollen lymph nodes, and sore arm18 101. More severe adverse events associated with ACAM2000 include myocarditis and pericarditis, occurring at a rate of approximately 1 in 175 vaccine recipients (about 570 per 100,000), as well as encephalitis, eczema vaccinatum, and ocular complications that can lead to blindness11 1328. Because ACAM2000 vaccination sites can shed live virus, there is a risk of transmission to unvaccinated contacts if proper care is not taken5 13.
Common side effects of monkeypox vaccines include:
- Pain, redness, swelling, hardness, and itching at the injection site26 8
- Fever, headache, tiredness, chills, and nausea26 3
- Local skin reactions such as bumps or lumps that may last days or weeks, especially after intradermal JYNNEOS administration17 8
- Rash and swollen lymph nodes, more common with ACAM200018 1
- Rare severe allergic reactions including anaphylaxis21 22
Managing Monkeypox Vaccine Reactions
Managing side effects from monkeypox vaccines primarily involves supportive care, which can alleviate symptoms and promote recovery10 22. Over-the-counter analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended to relieve pain, fever, and muscle aches10 22. Adequate hydration is also advised to help mitigate side effects and support the immune response16 22.
💡 Did You Know?
Severe and long-term side effects like myopericarditis have been reported to be found in approximately every 20 individuals out of 100,000 receiving ACAM200028 .
Intradermal administration of JYNNEOS, authorized under emergency use to extend vaccine supply, tends to cause less pain but may lead to more prolonged local skin reactions such as redness, itching, swelling, thickening, and discoloration of the skin at the injection site17 218. These reactions are generally mild and self-limited.
Severe allergic reactions or cardiac symptoms such as chest pain, palpitations, or shortness of breath after vaccination require urgent medical evaluation11 13. Myocarditis and pericarditis, while rare, are recognized adverse events associated with ACAM2000 vaccination and necessitate close monitoring and treatment if they occur13 . Because ACAM2000 vaccination sites can shed live virus, proper wound care and hygiene are essential to prevent transmission to others5 13.
Key steps to manage monkeypox vaccine side effects include:
- Use acetaminophen or NSAIDs to relieve pain, fever, and muscle aches10 22
- Maintain adequate fluid intake to support recovery16 22
- Monitor injection site for prolonged redness, swelling, or itching, especially after intradermal JYNNEOS17 21
- Seek urgent medical care for severe allergic reactions or cardiac symptoms11 13
- Follow proper wound care instructions after ACAM2000 vaccination to prevent virus transmission5 13
