Mpox After Two JYNNEOS Doses Is Rare and Milder, CDC Finds

By Sarah Anne J. Guagliardo and colleagues, CDC. Morbidity and Mortality Weekly Report (MMWR).

In brief

• Known: two doses of JYNNEOS vaccine prevent many mpox cases, but fully vaccinated people can still be infected.
• New: infection after 2 doses happened in fewer than 1% of fully vaccinated people, was milder, and occurred at widely varying times after vaccination — suggesting immunity is not waning.
• So what: people recommended for mpox vaccination should complete both doses; no additional doses are recommended.

Background

JYNNEOS, a replication-deficient vaccine approved as 2 doses against smallpox and mpox, was given to nearly everyone vaccinated in the U.S. during the global outbreak, which hit gay, bisexual and other men who have sex with men and transgender and nonbinary people hardest. Only about 25% of the at-risk population was fully vaccinated. A May 2023 cluster in Chicago, mostly among fully vaccinated people, raised questions: how often do such infections happen, do intradermal doses (favored when vaccine was scarce) protect as well, and are boosters needed?

The data

National case reports from May 11, 2022, to May 1, 2024: 32,819 mpox cases.

• Unvaccinated: 24,507 (75%).
• Fully vaccinated (2 doses, the second at least 14 days before illness): 271 (0.8%), 51 of them in 2024, from 27 jurisdictions.
• Rate: in 31 jurisdictions with near-complete data, 187 infections among 188,907 fully vaccinated people — 0.1%.

Share of mpox cases in fully vaccinated people, by week. Chart: CDC.

Who, and how sick

Compared with unvaccinated patients, fully vaccinated patients were:

• more often non-Hispanic White (59%) and aged 30–39 (47%);
• reporting more sex partners in the prior 21 days (median two vs one);
• less often living with HIV (29% vs 54%);
• less sick: less systemic illness (fever, headache, swollen glands and more), rash in fewer places (median one site vs four), though genital rash was more likely (odds ratio 2.3);
• rarely hospitalized (1.4% vs 8.4%), with no deaths (vs 56 among the unvaccinated).

Timing and route

Infections came a median 266 days after the second dose (14 to 621 days). Where both routes were known (139 people): 46% had mixed doses, 32% two subcutaneous doses, and 22% two intradermal doses. Among two-dose recipients of one route, infection came later after intradermal doses (median 363 days) than subcutaneous ones (263 days). The meaning is unclear, but it should boost confidence in intradermal doses.

What it means

• Rare and milder: consistent with other studies, whatever the route.
• Exposure matters: more partners among vaccinated cases suggest more chances for exposure; some vaccinated people may assume they're immune.
• Immunity: antibody levels fall after vaccination, but the varied timing of infections suggests protection persists; antibodies aren't the only marker of immunity.
• Coverage is low: only one in four eligible people is fully vaccinated. ACIP added JYNNEOS to the routine schedule for people at risk in October 2023; clinicians should offer it at routine visits.

Recommendations

• Get both doses; anyone whose first dose was more than 28 days ago should get the second as soon as possible.
• No booster is recommended now.
• Subcutaneous injection is preferred now that supply is adequate; earlier intradermal doses count and need not be repeated.
• Combine vaccination with other prevention: talk with partners about symptoms, watch for unexplained rashes, avoid close contact when sick, and pair with HIV and STI testing and care.
• Report vaccination status of cases to spot any waning immunity.

Limitations

Vaccination status was missing for 3,737 cases (11%); mild infections may go uncounted; small numbers limit subgroup comparisons; and sexual-exposure data were sparse.

Sources

Based on "Monkeypox Virus Infections After 2 Preexposure Doses of JYNNEOS Vaccine — United States, May 2022–May 2024," Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention; MMWR material is in the public domain.