Mpox disease severity reduced with pre-exposure JYNNEOS vaccination

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The administration of the modified vaccinia virus Ankara vaccine (JYNNEOS®) prior to mpox exposure is associated with reduced disease severity in cisgender men and boys, according to results of a study published in The Lancet Infectious Diseases.

The JYNNEOS vaccine is a third-generation, live-attenuated vaccine that was granted emergency use authorization by the United States Food and Drug Administration (FDA) following the global outbreak of mpox in 2022.

Researchers surveyed 4609 cisgender men and boys with laboratory-confirmed mpox reported to the California Department of Public Health between May 2022 and December 2023 to assess illness characteristics and JYNNEOS vaccination history.

Study patients were categorized by lesion distribution, with those in the case group having disseminated lesions across multiple anatomical sites and those in the control group having lesions confined to a single anatomical site. The researchers collected data on time of JYNNEOS receipt (pre-exposure vs post-exposure vaccination) and HIV status from all patients. They also compared outcomes between the groups to estimate vaccine effectiveness (VE) against hospitalization and mpox disease progression involving disseminated lesions.

Among patients with multisite lesions (n=3043) and control patients (n=1566), the median ages were 35 (IQR, 30-43) and 36 (IQR, 30-45) years, 47.9% and 38.1% were Hispanic, 47.3% and 34.5% had HIV infection, 19.4% and 15.5% reported tecovirimat use, and 86.4% and 74.8% were unvaccinated, respectively. In the control group, patients most commonly reported single-site lesions on the genitals (55.2%), buttocks (21.1%), or head (10.5%).

Overall, 3.7% of patients with multisite lesions and 18.2% of control patients received pre-exposure vaccination, with administration occurring a median of 47 (IQR, 28-318) days prior to mpox symptom onset. The estimated overall VE against disease progression was 58.8% (95% CI, 50.3-65.9). Stratified by receipt of partial and full pre-exposure vaccination series, the estimated VE was 57.6% (95% CI, 46.3-66.5) and 60.9% (95% CI, 47.1-71.1), respectively.

Of patients with multisite lesions and control patients who received post-exposure vaccination (7.0% and 9.3%, respectively), the median time of receipt was 5 (IQR, 3-8) days before symptom onset. Post-exposure vaccination was associated with an estimated overall VE of 15.9% (95% CI, 3.3-26.8). Moreover, the estimated VE of JYNNEOS decreased with later administration, with rates of 23.5% (95% CI, -9.7 to 46.6), 17.3% (95% CI, -3.2 to 33.7), and 8.1% (95% CI, -12.4 to 24.8) recorded when receipt occurred 10 to 13, 5 to 9, and 1 to 4 days before symptom onset, respectively.

Further analysis of pre-exposure vaccination outcomes by lesion location showed VE rates of 55.9% (95% CI, 44.3-65.1) for patients with genital lesions, 48.9% (95% CI, 32.6-61.3) for those with anal, rectal, or peri-anal lesions, and 58.3% (95% CI, 32.5%-74.2%) for those with lesions in other areas. In contrast, post-exposure vaccination was associated with protection against disease among only patients with genital lesions (VE, 20.9%; 95% CI, 3.5-35.3). In general, VE and number of affected regions were positively correlated.

Stratified by HIV status, the estimated VE of pre-exposure vaccination was higher in patients with HIV (66.6%; 95% CI, 56.8-74.0) than in those without HIV 44.8% (95% CI, 27.5-58.0). The researchers noted similar findings for post-exposure vaccination in patients with vs without HIV infection (VE, 24.8%; 95% CI, 7.8-38.6 vs 6.3%; 95% CI, -13.4 to 22.6). In regard to HIV characteristics, protection conferred by pre-exposure vaccination was limited to patients with CD4+ counts at or above 350 cells/µL (VE, 49.4%; 95% CI, 31.3-62.8).

In an analysis of severe mpox outcomes, pre-exposure vaccination was associated with protection against hospital admission (VE, 85.4%; 95% CI, 54.3-95.3), chills (VE, 57.0%; 95% CI, 46.7-65.3), fever (VE, 52.8%; 95% CI, 43.1-60.9), and lymphadenopathy (VE, 22.0%; 95% CI, 7.9-34.0). In contrast, post-exposure vaccination was only associated with protection against illness involving chills (VE, 17.2%; 95% CI, 2.2-29.9).

Study limitations include a population of only cisgender men and boys, small sample sizes, and self-reported symptoms.

The researchers concluded, “Securing high uptake of JYNNEOS is an important public health objective to mitigate [mpox virus] transmission and to lower individuals’ risk of severe disease if they are exposed to [mpox virus].”

By Jessica Nye, PhD

References:

Granskog L, Saadeh K, Lorenz K, et al. Effect of JYNNEOS vaccination on mpox clinical progression: a case–control study. Lancet Infect Dis. Published online May 21, 2025. doi:10.1016/S1473-3099(25)00180-X

 

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