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Over the last 2 years, most new cases of mpox in the U.S. occurred in unvaccinated people, and less than 1% occurred in people who were fully vaccinated against the disease, according to CDC data.

Among 32,819 U.S. mpox cases reported to the CDC from May 2022 to May 2024, only 0.8% occurred among people who had received two doses of the mpox vaccine Jynneos, while 75% of cases occurred among unvaccinated people, reported Sarah Anne Guagliardo, PhD, of the CDC's Mpox National Response Team, and colleagues in the .

"Despite a perceived increase in [mpox] infections among fully vaccinated persons during 2024, this report indicates that, to date, persistent vaccine-derived immunologic response among persons who received the 2-dose vaccine series exists," the authors wrote.

Of note, only 25% of people in the U.S. who are eligible for the Jynneos vaccine have received it. "Every opportunity should be taken to facilitate vaccination," Guagliardo and team noted, adding that "clinicians should remind patients that mpox is still circulating in the United States, and vaccination is an important tool to stopping the spread of mpox."

The researchers also found that infections among the fully vaccinated resulted in less severe illness. The odds of developing systemic illness with symptoms such as fever, headache, lymphadenopathy, malaise, abdominal pain, and myalgia were significantly lower among those who had received the full Jynneos series compared with those who were unvaccinated (P<0.05 for all).

In addition, only 1.4% of fully vaccinated people were hospitalized for mpox versus 8.4% of those who were unvaccinated (OR 0.2, 95% CI 0.0-0.5). None of the fully vaccinated people died, and 56 deaths occurred among unvaccinated mpox patients.

Mpox cases among fully vaccinated individuals occurred at a median 266 days after the second dose (range 14 to 621 days).

Infections in fully vaccinated people were more likely to occur among non-Hispanic white men (59%) and those ages 30 to 39 (47%), when compared with unvaccinated people (P<0.001 for both). Notably, fully vaccinated people reported a higher number of sexual partners (2, IQR 1-3) than unvaccinated people (1, IQR 1-2; P<0.001)

The report also examined vaccine route of administration. The FDA-approved regimen for Jynneos is 0.5 mL administered subcutaneously in a series of two doses given 28 days apart. During the height of the initial mpox outbreak in 2022, the Jynneos vaccine was in short supply and a lower 0.1 mL intradermal dose was recommended to preserve vaccine availability. However, questions arose about whether this dose and route of administration were effective.

Interestingly, Guagliardo and colleagues found that infections after full vaccination were more common in people who had received the shots by both the subcutaneous and intradermal route (46%) or the subcutaneous route (32%) compared with the intradermal route only (22%). Although there were no significant differences between those three groups, people who had received two intradermal doses had a longer median interval between the second dose and illness onset (363 days) when compared with people who received two subcutaneous doses (263 days, P<0.001).

"The significance of this observation is not known and requires further monitoring and study," the researchers wrote, pointing out that the findings should increase confidence about intradermal administration of the vaccine.

Now that there is no shortage of the vaccine, the CDC has said that Jynneos should be administered via the subcutaneous route, but previously administered intradermal vaccine doses can be considered effective.

One concern has been whether immunity from the mpox vaccine is waning, the authors noted. "Studies have indicated that vaccine titers decrease a few months after vaccination," they wrote. "However, the clinical significance of waning antibody levels is uncertain." Booster doses of the mpox vaccine are not recommended at this time.

In August 2022, the FDA issued an emergency use authorization (EUA) that allowed the use of the Jynneos vaccine to prevent mpox. that all adults in any age group who are at increased risk of becoming infected with mpox (e.g., men who have sex with men, those with a diagnosis of a sexually transmitted infection, and those with multiple sex partners, etc.) should receive a two-dose series of the vaccine.

Guagliardo and colleagues acknowledged that infections among the fully vaccinated may have been under-reported, since vaccination data were missing for 11% of nationally reported cases. Also, since mpox is often milder among the fully vaccinated, some cases may have not been evaluated or reported.

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