Severe mpox (formerly monkeypox) disease in five patients after recent vaccination with MVA-BN vaccine, Belgium, July to October 2022

Vaccination is important in containing the 2022 mpox (formerly monkeypox) epidemic. We describe five Belgian patients with localised severe symptoms of proctitis and penile oedema, occurring between 4 and 35 days after post-exposure preventive vaccination or after one- or two-dose off-label pre-exposure preventive vaccination with MVA-BN vaccine. Genome sequencing did not reveal evidence for immune escape variants. Healthcare workers and those at risk should be aware of possible infections occurring shortly after vaccination and the need for other preventive measures.

A homosexual couple between 30-50 years with a high-risk profile for acquiring monkeypox infection was invited for a subcutaneous vaccination with a full dose of Jynneos. One of the men was HIV-positive, the other under continuous HIV-PrEP treatment. They were vaccinated at the same day and had 23 days later both unprotected "bottom" and "top" anal sex with two other MSM and with each other. Both had no other partners during the three weeks before onset of symptoms. 6 days later, day 29 after the first dose, they received a second dose (1/5 dose Jynneos, intradermal administration). Symptoms started two and one day(s) after the second dose in case 2 and 3, respectively. Both reported mild unspecific symptoms without fever but rectal and anal pain with mucus secretion and bleeding. They presented at an emergency department in Antwerp. Painful small anal ulcers were detected in both cases. They were empirically treated with ceftriaxone and azithromycine. Screening for gonorrhoea and chlamydia was negative, anal swab for MPX was positive. They presented 12 and 13 days after onset of symptoms at ITM, the anal swabs were still positive (Ct 25.11 and Ct 35.75, respectively). The proctitis was healed without sequelae. Legend: The table shows the location of the SNV, amino acid changes in the involved proteins, and whether these are shared by any of the publicly available MPXV genomes from the outbreak in non-endemic countries with collection dates spanning mid August 2022 to mid October 2022 (downloaded from GISAID, https://www.gisaid.org, n = 479). To broaden this screen, the sequence of proteins with rather rare amino-acid substitutions (shared < 1%) was then used as query for the blastp tool (https://www.ncbi.nlm.nih.gov/) using the non-redundant database (NR), before aligning the resulting subjects using the COBALT tool (Constraint-based Multiple Alignment Tool, NCBI) to identify any other NCBI available protein sequence that shares the retrieved amino-acid substitutions.
The PPV Case 1 MPXV sequence shows a rather common (shared with 17/479 MPX sequences) R84K substitution in OPG016, a protein that contains an 'MHC class I-like antigen recognition-like superfamily'-domain (InterPro accession: 16397). The (immunologic) impact of the R84K substitution remains to be resolved.
The PPV Case 2 MPXV sequence shows non-synonymous mutations in OPG052 (R11Q) and OPG055 (D273N) that were not shared with sequences from the initial screen. The broader screen did identify two MPXV sequences that share each of these amino-acid substitutions. While OPG055 D273N was found in MPXV genome sequences from samples collected during the 2022 outbreak (OP415251.1 and OP536791.1), OPG052 R11Q could only be found in MPXV genome sequences from samples collected in the 1970's (DQ011156 .1 and KP849470 .1). A curated protein database search (https://www.ebi.ac.uk/interpro/ and https://www.uniprot.org/) did not reveal functional information for these two proteins. Of note, this MPXV genome also presented a non-synonymous mutation in OPG209 (E31K), a hypothetical protein, with low frequency in publicly available MPXV genomes (2 in the initial screen, 5 in the extended screen). Interestingly, although not unique to this MPXV genome sequence, a non-synonymous mutation was identified in protein OPG041, of which a role in IFN resistance has been shown [1]. Whether the E42K substitution results in a loss-or gain-of-function has yet to be described.
The PPV Case 4 MPXV sequence shows a non-synonymous mutation in OPG042 (G362E), a phospholipase D-like protein. Our screen did not identify other publicly available MPXV sequences that share this substitution. Of note, the gene coding for this protein was shown not to affect vaccinia virus replication nor virulence. [2,3] Supplementary Figure S1. Severity scale for monkeypox cases.
Internal use at ITM outpatient department to categorize disease severity based on international recommendations and own experiences.