The mpox vaccine is a shot that protects against mpox (formerly called monkeypox) by training your immune system to recognize and fight the virus before it can cause illness. Two vaccines are approved in the United States for this purpose: JYNNEOS and ACAM2000. In practice, only JYNNEOS has been used during recent outbreaks, and it’s the one most people will encounter.
JYNNEOS vs. ACAM2000
JYNNEOS is a newer, third-generation vaccine made from a weakened live virus that does not replicate efficiently in humans. That’s a key safety advantage: because the virus in the vaccine can’t copy itself well inside your body, the risk of serious side effects is much lower. JYNNEOS is manufactured by Bavarian Nordic and is also sold internationally under the names Imvamune and Imvanex. It’s the vaccine the CDC recommends for mpox prevention.
ACAM2000 is an older, second-generation vaccine that contains a live virus which does replicate in humans. It was originally designed for smallpox and carries a higher risk of side effects, including a small but real risk of heart inflammation. Because of that safety profile, ACAM2000 is only available for mpox under a special investigational protocol and isn’t routinely offered. For nearly everyone seeking mpox protection, JYNNEOS is the vaccine you’ll receive.
How Well It Works
JYNNEOS is given as two doses, spaced about four weeks apart. After the first dose alone, effectiveness against diagnosed mpox infection is roughly 68%. After both doses, that jumps to about 89%, based on a CDC study conducted in New York during the 2022 outbreak. The combined effectiveness for people who received at least one dose was approximately 76%.
Those numbers make a strong case for completing both shots. A single dose provides meaningful protection, which matters if you’ve recently been exposed and need rapid defense, but the second dose nearly doubles the gap between you and infection. Protection isn’t considered complete until about two weeks after the second dose, so timing matters if you’re planning around a specific risk window.
Who Should Get Vaccinated
The mpox vaccine isn’t recommended for the general population. The CDC targets it toward people at higher risk of exposure. You’re a candidate if any of the following apply:
- Known or suspected exposure: You’ve had contact with someone diagnosed with mpox, or a sex partner in the past two weeks received an mpox diagnosis.
- Sexual risk factors: You’re a gay, bisexual, or other man who has sex with men, or you’re transgender or nonbinary, and in the past six months you’ve had more than one sex partner, a new sexually transmitted infection diagnosis, sex at a commercial venue like a bathhouse or sex club, or sex connected to a large event in an area with active mpox transmission.
- Partner risk: Your sex partner meets any of the criteria above.
- Travel: You’re traveling to a country experiencing a clade I mpox outbreak and anticipate sexual contact with new partners, at commercial venues, or in connection with large public events.
- Occupational exposure: You work in a laboratory or healthcare setting where you may encounter orthopoxviruses.
You can also get vaccinated if you anticipate any of these scenarios in the near future, even if they haven’t happened yet. The vaccine works best when your immune system has time to build a response before exposure, so getting vaccinated ahead of time is ideal.
Post-Exposure Vaccination
JYNNEOS can also be given after a known exposure to mpox, a use called post-exposure prophylaxis. The goal is to give your immune system a head start so it can fight the virus before symptoms develop. The sooner you get vaccinated after exposure, the better your chances of preventing illness or at least reducing its severity. If you know or suspect you’ve been exposed, contacting a healthcare provider promptly is the most important step.
What to Expect After the Shot
JYNNEOS side effects are typical of most vaccines and generally mild. The most common reactions are at the injection site: redness, soreness, swelling, and itching. Some people also experience fatigue, headache, or muscle pain in the days following vaccination. These effects tend to resolve on their own within a few days.
Compared to ACAM2000, JYNNEOS has a notably gentler side effect profile. There’s no open wound at the injection site (ACAM2000 is given by pricking the skin and produces a visible sore), and the risks of serious cardiac and other complications are substantially lower. This is one of the main reasons JYNNEOS has become the default choice for mpox vaccination.
How the Vaccine Actually Works
Mpox belongs to a family of viruses called orthopoxviruses, which also includes smallpox. These viruses are similar enough that immunity to one provides strong cross-protection against the others. This is the same principle behind the original smallpox vaccine, which used a related virus (cowpox) to protect against smallpox centuries ago.
JYNNEOS uses a modified version of a virus in this same family. When injected, it exposes your immune system to viral proteins without causing disease. Your body produces antibodies and trains immune cells to recognize those proteins. If you later encounter the actual mpox virus, your immune system is already primed to respond quickly, either preventing infection entirely or limiting it to a milder course.
People who received the older smallpox vaccine (routinely given in the U.S. until 1972) may still have some residual cross-protection against mpox, though immunity from decades-old vaccination has likely waned significantly.