Human Monkeypox Virus Infection in the Immediate Period After Receiving Modified Vaccinia Ankara Vaccine

The current global outbreak of monkeypox virus has led to 59 179 cases as of September 13, 2022.¹ Among US cases, 96.9% have occurred in men and 78.9% in men who reported male-to-male sexual or intimate contact, mirroring international trends.² Modified Vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN, JYNNEOS) is a live, nonreplicating vaccine indicated for prevention of smallpox and monkeypox infection in adults.³ While immunogenicity data suggest robust response rates after the 2-dose series (100% at 2 weeks),⁴ data on effectiveness in clinical use are limited. Because local health departments are challenged with limited MVA-BN availability, many have implemented a single-dose strategy to maximize current supply; further strategies to deliver lower-volume doses intradermally have also been adopted. We describe monkeypox infections after a single dose of MVA-BN among the largest monkeypox testing and vaccination site in the US Midwest.

In May 2022, Howard Brown Health (HBH) began performing real-time reverse transcriptase–polymerase chain reaction (RT-PCR) tests to detect monkeypox (Illinois Department of Public Health Division of Laboratory Services Non-variola Orthopoxvirus RT-PCR assay, Quest Diagnostics Monkeypox Virus DNA RT-PCR assay). HBH began administering MVA-BN to eligible individuals on June 28, 2022. Patients who tested positive for monkeypox at least 1 day after receiving the first dose of the MVA-BN from June 28, 2022, through September 9, 2022, were included.

All positive monkeypox cases during the study period were extracted from the electronic medical record (EMR). Vaccination status was then obtained through the EMR and review of an electronic, statewide immunization record-sharing database. Confirmed positive monkeypox cases after vaccination were stratified by days to positivity (1-7 days, 8-14 days, 15-28 days, and >28 days). Demographic data, HIV status and virologic suppression, and HIV preexposure prophylaxis use were extracted from the EMR. As a quality assessment of internal monkeypox testing and vaccination outcomes, the HBH institutional review board determined the study did not require approval.

During the study period, 400 patients tested positive for monkeypox, and 7339 individuals received their first dose of MVA-BN at HBH. Ninety patients tested positive for monkeypox at least 1 day after vaccination (Table 1) with a median age of 33 years (IQR, 29-41; range, 24-69 years); 91% were cisgender men, 37.8% were living with HIV, and 73.5% had viral loads less than 200 copies/mL.

Thirty-seven and 32 cases occurred 1 to 7 and 8 to 14 days after vaccination, respectively, comprising 77% (69/90) of all postvaccination cases. The median time between vaccination and infection was 8.5 days (IQR, 4-13; range, 1-58 days). Of the cases 1 to 14 days after vaccination, 36.2% (25/69) were people with HIV, of whom 96% (24/25) were virologically suppressed. Fifty-four percent (24/44) of early postvaccination cases without HIV infection were using preexposure prophylaxis.

Eight monkeypox cases occurred more than 28 days from the first dose of MVA-BN, of which 2 cases occurred more than 14 days from the second dose (Table 2). All 8 patients self-identified as cisgender males, 50% (4/8) had HIV, all of whom were virologically suppressed. All patients except 1 had fewer than 10 lesions. One patient was given tecovirimat antiviral therapy due to the severity of anogenital symptoms.

In this small study, the majority of postvaccination monkeypox infections occurred within 2 weeks of receiving the first dose of MVA-BN, before full effectiveness was likely to have been achieved, in line with published immunogenicity data.^4,5 Because the incubation period for monkeypox is 3 to 17 days, some of the cases occurring between 1 and 14 days after vaccination may not represent true vaccine failure because patients may have sought vaccination after realizing they were exposed. Of concern is that at least 2 breakthrough infections were observed in individuals at least 3 weeks after a second dose.

Limitations of the study include the small number of patients; the involvement of a single site; and due to the recency of vaccine rollout, the postvaccination observation period was not uniform across the cohort. Nonetheless, these data support public health messaging around behavior modification and risk reduction counseling in the immediate postvaccination period. Larger studies are needed to better understand vaccine effectiveness and durability of immune response with MVA-BN against monkeypox in clinical use.

Accepted for Publication: September 19, 2022.

Published Online: September 30, 2022. doi:10.1001/jama.2022.18320

Corresponding Author: Aniruddha Hazra, MD, Howard Brown Health, 5841 S Maryland Ave, MC5065, Chicago, IL 60637 (anuh@howardbrown.org).

Author Contributions: Dr Hazra had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hazra, Hedberg.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Hazra, Hedberg.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hazra, Rusie, Hedberg.

Administrative, technical, or material support: Hazra, Schneider.

Conflict of Interest Disclosures: None reported.