Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara-Bavaria Nordic vaccine against mpox in children: a national outbreak response

Shamez N Ladhani*, Alexander C Dowell, Scott Jones, Bethany Hicks, Cathy Rowe, Jusnara Begum, Dagmar Wailblinger, John Wright, Stephen Owens, Ailsa Pickering, Benjamin Shilltoe, Paddy McMaster, Elizabeth Whittaker, Jianmin Zuo, Annabel Powell, Gayatri Amirthalingam, Sema Mandal, Jamie Lopez-Bernal, Mary E Ramsay, Neave KissaneMichael Bell, Heather Watson, David Ho, Bassam Hallis, Ashley Otter, Paul Moss, Jonathan Cohen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

BACKGROUND: In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children.

METHODS: This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox.

FINDINGS: Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination.

INTERPRETATION: A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response.

FUNDING: UK Health Security Agency.

Original languageEnglish
Pages (from-to)1042-1050
Number of pages9
JournalThe Lancet Infectious Diseases
Volume23
Issue number9
Early online date16 Jun 2023
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Acknowledgments:
This study was internally funded by the UK Health Security Agency, with funding previously obtained from Coalition for Epidemic Preparedness Innovations for monkeypox serology assay development. We would like to thank the children and their families for volunteering to take part in this study.

Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Keywords

  • Humans
  • Male
  • Child
  • Child, Preschool
  • Female
  • Vaccinia
  • Monkeypox
  • Vaccinia virus
  • Smallpox Vaccine/adverse effects
  • Immunity, Cellular
  • Antigens, Viral
  • Disease Outbreaks/prevention & control
  • Antibodies, Viral

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