Berlin, 19 March 2025
Just one dose of the smallpox vaccine Imvanex provides 84 per cent protection against Mpox. This is the result of a study by Charité – Universitätsmedizin Berlin. In people with HIV, however, protection is still inadequate after one dose of the vaccine. All risk groups, but especially people with HIV, should therefore receive the recommended second dose of the vaccine. The results have now been published in the specialist journal The Lancet Infectious Diseases*.
Since a wave of infection spread the Mpox virus globally in 2022, the Standing Committee on Vaccination (STIKO) has recommended that people with an increased risk of Mpox be vaccinated with the Imvanex vaccine. Originally developed to protect against true smallpox, the vaccine was also authorised by the European Medicines Agency (EMA) in July 2022 to protect against Mpox in view of the health emergency. The Mpox virus is related to the original smallpox virus (Variola major). The authorisation was based on laboratory data showing that the vaccination provides so-called cross-protection. However, the extent of the protective effect, particularly in risk groups, has not yet been clarified.
Comprehensive study with more than 9,300 participants
On behalf of the EMA, a team led by Prof. Leif Erik Sander, Director of the Department of Infectious Diseases and Intensive Care Medicine at Charité and Head of the Personalised Infection Medicine working group at the Berlin Institute of Health at Charité (BIH), has now investigated the effectiveness of the vaccination against Mpox in a comprehensive study and compared it for the first time for people with and without HIV. ‘Our results confirm that just one dose of vaccine provides good protection against Mpox, at least in the short term,’ says the infectiologist. ‘However, this only applies to people who are not living with HIV. In people with HIV – even if they are taking effective medication – we unfortunately do not see a sufficient protective effect after one dose of the vaccine.’
Between July 2022 and December 2023, more than 9,300 men or trans people who reported having sex with changing men or trans people took part in the study. They belong to the groups of people for whom vaccination is recommended by the STIKO. Half of the participants received a dose of the Imvanex vaccination, while the other half remained unvaccinated. For both groups, the average number of people infected with Mpox was recorded over a period of almost two months.
One dose protects immunocompromised people
In the test subjects without HIV, there were significantly fewer cases of Mpox in the vaccinated group than in the unvaccinated group, with a protective effect of 84 per cent. ‘This is a very good value, which will probably be further increased by the second vaccination dose,’ says Leif Erik Sander. However, due to the sharp decline in infections in the second half of 2022, the additional effect of the second vaccine dose could not be determined in the study.
In contrast, people living with HIV only showed a small protective effect, which was not statistically significant. ‘The reason is probably that certain immune cells, the T cells, are needed to build up immune protection after the vaccination,’ explains the physician. ‘In people with HIV, these T cells are often reduced and not fully functional, so the immune response is weaker. Our observation that they experienced fewer local and systemic side effects after the vaccination is also consistent with this.’
Two vaccine doses recommended for everyone, especially for people with HIV
‘We assume that people with HIV will develop protection against Mpox after the second vaccine dose and strongly recommend that they receive the two vaccine doses recommended by the STIKO,’ emphasises Prof Florian Kurth. The head of the Clinical Infection Research Group at Charité was in charge of the study together with Leif Erik Sander. ‘We also recommend that all other risk groups complete the two vaccinations. The immune system typically builds up longer-lasting immune protection if it has been exposed to the vaccine more than once.’ Further studies will have to show exactly how high the protective effect will be in the different groups of people after two vaccinations.
The research team observed that vaccinated people showed less severe symptoms if they nevertheless contracted the virus: They developed fewer smallpox on the skin, which also healed more quickly, and were less likely to report systemic signs of illness such as fever. ‘We assume that the second vaccination will further reduce the severity of the symptoms,’ says Florian Kurth. ‘With less smallpox, the risk of transmission of the virus will presumably also decrease. A complete vaccination should therefore counteract a resurgence of Mpox outbreaks.’
Vaccination is well tolerated
The researchers also analysed the tolerability and safety of the Mpox vaccination in over 6,500 people. The most common vaccination reaction reported by the test subjects was pain at the injection site. Less than three per cent of those vaccinated reported stronger sensations such as fever, headache, muscle pain, nausea or diarrhoea. ‘The Mpox vaccination is therefore safe and well tolerated overall,’ summarises Florian Kurth. ‘It should be noted that vaccination protection is only fully established after around 14 days. In addition, general preventive measures such as the use of condoms should be taken – also to protect against other sexually transmitted diseases.’
As clade IIb of the Mpox virus was circulating in Germany during the study period, the results on vaccine protection apply to this virus lineage. However, due to the high degree of relatedness to clade I, which is currently rampant in Central Africa and neighbouring regions, the researchers assume a very high level of cross-protection. According to them, the study results are therefore also likely to be relevant for the current clade I outbreak in Africa. It is still unclear how long the vaccine protection will last. In the next step, the research team is planning long-term studies and also wants to investigate the effect of a third vaccine dose.
*Hillus D et al. Safety and effectiveness of MVA-BN vaccination against Mpox: A combined prospective and retrospective cohort study (SEMVAc/TEMVAc). Lancet Infect Dis 2025 Mar 18. doi: 10.1016/S1473-3099(25)00082-9
About Mpox
Mpox (until 2022: monkeypox) is caused by the monkeypox virus, which is related to the human smallpox viruses. The clinical picture is similar to that of true smallpox, which has been considered eradicated since 1980. Whereas smallpox was a life-threatening infectious disease, Mpox is generally milder. It causes fever, headache, muscle and back pain, and the lymph nodes swell. A few days later, pustules form on the skin or mucous membranes. These pustules can sometimes be very itchy and painful. Fatal cases are very rare and mainly affect children and immunocompromised people. However, severe courses of the disease can lead to severe scarring and long-term damage. The Mpox virus is transmitted through close physical contact.
The Mpox virus is categorised into clades based on genetic differences. In May 2022, there was a global outbreak of clade IIb, in which the virus spread primarily through close physical contact and sexual contact. Since then, more than 100,000 cases have been recorded in 122 countries. While the incidence of infection has declined significantly in Europe since autumn 2022, in some countries such as the USA, Brazil and Australia, well over 1,000 cases were recorded in 2024. New clade IIb cases are currently being reported in Australia, South Africa and South America. Since 2023, an increasing number of clade I Mpox infections (including a new variant Ib) have also been registered in Africa, particularly in the Democratic Republic of the Congo. The World Health Organisation (WHO) declared a public health emergency of international concern (PHEIC) for the clade II outbreak in 2022 and for the clade I outbreak in 2024.
About the Mpox vaccine
The Standing Committee on Vaccination (STIKO) recommends Mpox vaccination with the vaccine Imvanex, which is authorised in the EU. It has been authorised for protection against smallpox since 2013 and for protection against Mpox since July 2022. In the USA and Canada, it has been authorised against Mpox for several years under the vaccine names Jynneos and Imvamune respectively. It is a live vaccine with viruses that are not capable of reproducing in humans. The preparation is based on an attenuated cowpox virus (modified vaccinia virus Ankara, MVA vaccine), which is regarded as a kind of prototype of smallpox viruses and can therefore also provide cross-protection against other smallpox viruses. The groups recommended for vaccination include men aged 18 and over who have sex with men and frequently change partners, as well as laboratory staff who work with infectious Mpox samples. Basic immunisation is carried out with two vaccine doses.
About the study
The study was divided into two study arms in order to determine the tolerability and efficacy of the Mpox vaccination. Around 6,500 people were prospectively examined and regularly interviewed to determine safety and tolerability. A rolling cohort design was used in a so-called target trial to determine efficacy, which simulates a randomised clinical trial by retrospectively comparing the data of over 9,300 vaccinated and unvaccinated people with comparable demographic and clinical characteristics. Across the entire group of participants – i.e. with or without HIV – there was an average protective effect of 58 per cent. The study was funded by the BIH and the EMA.