Effect of JYNNEOS vaccination on mpox clinical progression: a case-control study

The JYNNEOS modified vaccinia virus Ankara vaccine is effective in preventing clade IIb mpox disease. However, vaccine effects on mpox severity are poorly understood. We aimed to assess associations between reported clinical characteristics and vaccination status among individuals with laboratory-confirmed mpox.

We conducted a case-control study using data collected from public health surveillance interviews of people with mpox in California. Eligible participants for primary analyses were men who were cisgender and participated in telephone interviews with complete responses recorded about anatomical sites where they had lesions. We estimated JYNNEOS vaccine effectiveness against progression to disease involving disseminated lesions via the adjusted odds ratio of vaccination, comparing participants who reported lesions disseminated across multiple anatomical regions (cases) with participants who reported lesions contained to a single anatomical region (controls). We used the same case-control framework to estimate vaccine effectiveness against progression to hospitalisation and prodromal symptoms.

Men who were cisgender represented 5763 (94·3%) of 6112 people reported to have laboratory-confrimed mpox in California from May 12, 2022, to Dec 31, 2023, among whom, 4609 (79·9%) met eligibility criteria and were included in primary analyses. Of 4609 participants, 1566 (34·0%) were classified as controls and 3043 (66·0%) were classified as cases. Among 3043 cases, 114 (3·7%) received pre-exposure vaccination and 214 (7·0%) received post-exposure vaccination only. Among 1566 controls, 285 (18·2%) received pre-exposure vaccination and 146 (9·3%) received post-exposure vaccination only. For pre-exposure vaccination, vaccine effectiveness against progression was 58·8% (95% CI 50·3-65·9); for post-exposure vaccination, vaccine effectiveness against progression was 15·9% (3·3-26·8). Pre-exposure vaccine effectiveness against progression was 66·6% (56·8-74·2) among people negative for HIV and 44·8% (27·5-58·0) for those with HIV. Pre-exposure vaccination was also associated with protection against progression to severe illness necessitating hospitalisation (85·4% [95% CI 54·3-95·3]), and with reduced odds for fever, chills, and lymphadenopathy.

Among men who were cisgender with mpox, pre-exposure vaccination with JYNNEOS was associated with less severe illness. Awareness of an attenuated disease phenotype involving localised lesions without accompanying prodromal symptoms is needed to ensure accurate diagnosis of mpox in previously vaccinated individuals.

The California Department of Public Health and the US National Institutes of Health.