Since the multi-country mpox outbreaks in 2022, the smallpox vaccine MVA-BN has been widely deployed to protect against mpox disease, with pressures on global supply levels.
Providing insights for improved vaccination strategies, PSI researchers and colleagues have now confirmed that smaller doses of MVA-BN trigger an immune response in the body if administered in a two-dose regimen. Additionally, they have worked out why these smaller doses may be more or less effective in different individuals or at-risk groups.
Recently published in The Lancet Microbe, the latest article from the IMOVA study was co-authored by colleagues across multiple University of Oxford departments, including the Pandemic Sciences Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Jenner Institute, and Weatherall Institute of Molecular Medicine, in collaboration with the UK Health Security Agency (UKHSA).
PSI Investigator Dr Nicholas Provine, co-first author, said: “The MVA-BN vaccine is critical in our efforts to protect against mpox, and this study provides key insights into the strengths and limitations of dose-sparing regimens designed to make limited vaccine supplies stretch further.”
Background
Mpox is a zoonotic disease caused by the Monkeypox virus (MPXV), which belongs to the orthopoxvirus genus.
A neglected disease until recently, mpox was declared a Public Health Emergency of International Concern by the World Health Organisation following a multi-country outbreak caused by the emergence of IIb MPXV in 2022; and a subsequent outbreak of increased severity, caused by MPXV clade Ib, in the Democratic Republic of the Congo and neighbouring countries.
The epidemic potential of mpox highlights the urgent need for effective prevention and control strategies. These include the use of repurposed smallpox vaccines such as MVA-BN (Modified vaccinia Ankara, manufactured by Bavarian Nordic) to prevent mpox disease.
Key research findings
The observational study recruited 34 participants among patients attending a sexual health vaccination clinic in Oxford. In accordance with guidance from the UK Joint Committee on Vaccination and Immunisation (JCVI), most participants received two fractionated doses of MVA-BN (0.1 mL per dose), administered intradermally.
The researchers contextualised the immune responses induced by this alternative regimen versus standard dosing (two doses of 0·5 mL each, administered subcutaneously), finding that:
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Only 50% of participants developed an antibody response (i.e., seroconvert) after one MVA-BN dose.
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A second dose resulted in antibody responses in 89% of participants, but those who took two doses to develop an antibody response had lower antibody levels.
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Lack of antibody response after one MVA-BN vaccine dose was associated with higher levels of inflammatory signatures in the blood prior to vaccination.
NDORMS Senior Clinical Research Fellow Dr Philip Drennan, Chief Investigator of the IMOVA study, said: “I am incredibly grateful to our funders, collaborators, and study participants for contributing to this vital work. We hope this study will spur future research deciphering the interplay between host immunity and vaccine protection, and ultimately help us develop better vaccine strategies for mpox.
“This is particularly relevant to individuals with pre-existing inflammatory conditions – such as people living with HIV, one of the groups most at risk during the 2022 outbreaks.”
Read the paper in The Lancet Microbe.