Clinical features of mpox in fully vaccinated people in New South Wales, Australia: an outbreak investigation and retrospective cohort study

<h2>Summary</h2><h3>Background</h3> Since 2022, clade IIb mpox outbreaks have occurred in non-endemic countries, primarily among men who have sex with men. WHO currently recommends two doses of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine at least 4 weeks apart for people at risk of infection. Infections in fully vaccinated people have been infrequently reported, and the clinical significance of waning vaccine-induced antibodies is unknown. We aimed to determine whether vaccination was associated with attenuated disease. <h3>Methods</h3> We conducted an outbreak investigation and retrospective cohort study of people with mpox notified in New South Wales, Australia between June 20 and Nov 20, 2024, using routinely collected data extracted from the statewide surveillance system. As part of routine practice, people with mpox and clinicians were interviewed. People were classified as fully vaccinated when they had received two MVA-BN doses at least 14 days before symptom onset and partially vaccinated when they had received one dose. Risk ratios were calculated by the number of MVA-BN doses for the following clinical outcomes: anogenital lesions (ie, genital, perianal, buttock, or groin lesions or symptoms suggestive of involvement of the rectal or urethral mucosa), extragenital lesions (those present at any other site), systemic symptoms (at least one of the following: fever, lymphadenopathy, myalgia, arthralgia, backache, or headache), and hospitalisation (admission for inpatient management of mpox). A subset of mpox genomes were sequenced including all samples collected during Aug 17–24, 2024, with a monkeypox virus polymerase chain reaction cycle threshold of 25 or lower, and samples from individuals who were deemed to be at risk of clade I monkeypox virus infection. <h3>Findings</h3> During the study period, 674 people (673 [99%] assigned male at birth and 669 [99%] identified as men; 17 [3%] identified as Aboriginal or Torres Strait Islander) were diagnosed with mpox (excluding one reinfection). The median age was 36 years (IQR 31–44). Vaccination status was ascertained for 663 (98%) of 674 people, with 251 (37%) of 674 being fully vaccinated, 72 (11%) partially vaccinated, and 340 (50%) not vaccinated. In fully vaccinated people, the median time between dose two and symptom onset was 21·8 months (IQR 19·5–23·0). Compared with unvaccinated people, fully vaccinated people were less likely to be hospitalised (risk ratio 0·11 [95% CI 0·03–0·43]), have extragenital lesions (0·45 [0·36–0·56]) or systemic symptoms (0·72 [0·64–0·80]); however, they were more likely to have anogenital lesions (1·11 [1·05–1·18]). Sequencing of 102 (15%) of 674 outbreak cases showed they were all clade IIb. <h3>Interpretation</h3> A two-dose MVA-BN series continued to protect against extragenital lesions, systemic symptoms, and hospitalisation beyond the point at which antibodies have been found to wane. <h3>Funding</h3> None.