Now is the time to launch mpox vaccine booster trials
December 11, 2025
The resurgence of mpox in major U.S. cities such as Los Angeles, New York, and Chicago underscores an urgent need for renewed public health research and action. With Clade I mpox now appearing in Los Angeles through local transmission, questions about booster vaccination are growing, yet data remain scarce. Despite evidence of strong initial protection from the two-dose Jynneos vaccine, the durability of immunity is still unclear. Federal leadership has waned, and vital studies on boosters remain unfunded. Empowering community-led research and funding clinical trials must become priorities to strengthen prevention, protect vulnerable populations, and prepare for sustained mpox circulation.
Mpox’s reemergence in Los Angeles, New York, and Chicago marks a troubling shift in the United States’ epidemic trajectory. The detection of locally transmitted Clade I cases in Los Angeles, a strain linked to Central Africa’s ongoing outbreak, highlights that mpox remains a persistent global and domestic threat. While case counts remain far below the 2022 emergency, community concerns are rising once again—particularly around whether booster vaccinations are needed and when they should be administered.
Despite widespread vaccination with Jynneos, data on long-term protection remain incomplete. The vaccine, derived from smallpox formulations, has proven highly effective at reducing infection and disease severity, but immunity’s durability beyond two years is uncertain. Unpublished CDC research suggests protection may last up to five years, yet antibodies appear to wane within the first year. Alarmingly, roughly one-third of new cases occur in previously vaccinated individuals.
Public health researchers argue that booster doses could strengthen long-term protection, especially in high-risk communities. However, federal research has stagnated. The CDC’s recent downsizing and reversion to stigmatizing “monkeypox” language have further hindered progress. Clinical trials are the only way to determine booster efficacy, yet they require significant funding and recruitment—resources that are currently lacking.
Given persistent community transmission, cities like Los Angeles and New York are ideal sites for a booster efficacy trial. Local governments, public health collaboratives, and private funders must fill the gap left by federal inaction. The queer community’s leadership during the 2022 outbreak proved vital in driving behavior change and scientific engagement. Renewed investment in community-driven research is essential to ensure accurate, destigmatized guidance and durable protection against mpox. Without proactive booster research, the U.S. risks repeating the same pattern of delayed response that allowed mpox to spread unchecked three years ago.