By Hendra Lukman 
A landmark study conducted at Charité – Universitätsmedizin Berlin has delivered crucial insights into the effectiveness of the Imvanex vaccine against Mpox, revealing a robust 84% protection rate in a single dose for the general at-risk population. However, the research also underscores a significant vulnerability: individuals living with HIV, even those on effective treatment, do not achieve sufficient protection from a single dose. These findings, published in the prestigious journal The Lancet Infectious Diseases, strongly advocate for the recommended two-dose vaccination regimen for all at-risk groups, with particular urgency for people with HIV.
The global resurgence of Mpox, initially known as monkeypox, in 2022 prompted swift action from public health authorities worldwide. In response to the burgeoning epidemic, Germany’s Standing Commission on Vaccination (STIKO) issued recommendations for vaccination with Imvanex for individuals identified as being at an elevated risk of infection. This vaccine, originally developed to combat smallpox, received approval from the European Medicines Agency (EMA) for Mpox protection in July 2022, acknowledging its potential to confer cross-protection against the related Mpox virus (variola major). While laboratory data supported this cross-protective capability, the real-world effectiveness, especially within vulnerable populations, remained a critical question until this comprehensive study.
Unveiling Vaccine Efficacy: A Large-Scale Investigation
The EMA commissioned a substantial study, led by Professor Leif Erik Sander, Director of the Department of Infectious Diseases and Critical Care Medicine at Charité and a research group leader at the Berlin Institute of Health at Charité (BIH). This research was designed to definitively assess the vaccine’s efficacy against Mpox, notably comparing its performance in individuals with and without HIV for the first time.
"Our results confirm that a single dose of the vaccine provides good protection against Mpox, at least for a short time," stated Professor Sander. "However, this only applies to people not living with HIV. Unfortunately, we found that people with HIV – even those taking adequate medication – are not sufficiently protected by a single dose."
The extensive study, conducted between July 2022 and December 2023, enrolled over 9,300 men and transgender individuals who reported engaging in sexual activity with men or transgender individuals. These demographics align with the groups identified by STIKO as being at higher risk and therefore recommended for vaccination. The participants were divided into two cohorts: half received a single dose of the Imvanex vaccine, while the other half served as an unvaccinated control group. Both groups were followed for an average of two months to meticulously track the incidence of Mpox infections.
Single Dose Success for HIV-Negative Individuals
The findings for HIV-negative participants were highly encouraging. The vaccinated cohort exhibited significantly fewer Mpox cases compared to their unvaccinated counterparts, translating to an impressive 84% vaccine effectiveness.
"That is a very good figure, which is likely increased even further by the second vaccine dose," Professor Sander commented. While the study design did not permit a definitive assessment of the additional benefit of a second dose due to a notable decline in Mpox infections in the latter half of 2022, the initial single-dose effectiveness for this group was a significant public health success.
The Critical Differentiator: HIV and Immune Response
The study’s findings diverged sharply when examining individuals living with HIV. In this group, a single dose of Imvanex showed only a marginal, statistically insignificant protective effect.
Professor Sander elaborated on the underlying immunological reasons: "The reason is presumably that developing immune protection after vaccination requires specific immune cells called T cells. These T cells often appear at lower levels in people with HIV and are not fully functional, which translates to a weaker immune response. This also corresponds to our observation that these participants experienced fewer local and systemic side effects after receiving the vaccine." This observation of reduced side effects in people with HIV after vaccination is an important indicator that their immune system may not be mounting as robust a response, further emphasizing the need for a more comprehensive vaccination strategy.
The Imperative of a Two-Dose Regimen
Professor Florian Kurth, Head of the Clinical Infection Research Group at Charité, who co-led the study with Professor Sander, underscored the critical importance of completing the two-dose vaccination schedule.
"We assume that people living with HIV develop protection against Mpox after the second vaccine dose, and urgently advise these people to receive the two vaccine doses recommended by the STIKO," Professor Kurth emphasized. "We recommend that people in all other at-risk groups also complete the two-dose regimen. The immune system typically develops longer-lasting immune protection when exposed to the vaccine on more than one occasion."
The study also provided insights into symptom severity. Vaccinated participants who still contracted Mpox experienced milder symptoms, characterized by fewer and more rapidly healing pox lesions, and a reduced likelihood of systemic symptoms such as fever. Researchers hypothesize that a second vaccine dose could further mitigate these symptoms and, consequently, reduce the risk of viral transmission. "Fewer pox lesions presumably also reduces the risk of transmitting the virus. Full vaccination should therefore ward off Mpox outbreaks," Professor Kurth added.
Vaccine Safety and Tolerability Profile
Beyond efficacy, the research also rigorously assessed the tolerability and safety of the Imvanex vaccine in over 6,500 individuals. The most frequently reported adverse event was localized pain at the injection site. More pronounced systemic symptoms, including fever, headache, muscle pain, nausea, or diarrhea, were reported by less than 3% of vaccinated participants.
"The Mpox vaccine is, therefore, safe and well tolerated overall," Professor Kurth summarized. "It is important to note that immune protection develops fully around 14 days after vaccination. In addition, people should take general preventive measures, such as using condoms – including to protect against other sexually transmitted diseases." This reinforces the understanding that vaccination is a crucial component of a multi-faceted prevention strategy.
Broader Implications and Future Directions
The findings of this study are directly relevant to Clade IIb of the Mpox virus, which was prevalent in Germany during the study period. Given the close genetic relationship between Clade IIb and Clade I, currently circulating in Central Africa, the researchers anticipate a high degree of cross-protection. This suggests the study’s outcomes could also inform strategies for addressing the ongoing Clade I outbreak in Africa.
The duration of vaccine-induced immunity remains an open question. The research team has outlined plans for long-term studies to investigate this aspect and to explore the potential benefits of a third vaccine dose, particularly for individuals with compromised immune systems.
Understanding Mpox: A Public Health Concern
Mpox, previously known as monkeypox, is a viral illness caused by the Mpox virus, a close relative of the variola virus that caused smallpox. While symptoms bear similarities to smallpox, Mpox generally presents a milder clinical course. Typical symptoms include fever, headache, muscle pain, backache, and swollen lymph nodes, followed by the appearance of pustules on the skin and mucous membranes, which can be intensely itchy and painful. Mpox-related fatalities are rare, primarily affecting children and immunocompromised individuals, but severe cases can lead to significant scarring and long-term health consequences. Transmission occurs through close physical contact.
The global outbreak of Clade IIb Mpox, which began in May 2022, spread rapidly through close and sexual contact, resulting in over 100,000 reported cases across 122 countries. While infection rates have decreased in Europe since late 2022, concerning increases in cases have been observed in countries like the USA, Brazil, and Argentina in 2024. Simultaneously, Clade I Mpox infections, including a new Ib variant, have seen a rise in Africa, particularly in the Democratic Republic of the Congo, leading the World Health Organization (WHO) to declare public health emergencies for both clades.
The Imvanex Vaccine: A Key Tool in Prevention
Imvanex, an EMA-approved vaccine, is recommended by Germany’s STIKO for Mpox prevention. Originally approved for smallpox in 2013, its use for Mpox was authorized in July 2022. It is also available in the USA and Canada as Jynneos and Imvamune, respectively. This live-attenuated vaccine utilizes a modified vaccinia virus Ankara (MVA) strain, a weakened cowpox virus, designed to induce cross-protection against other pox viruses. STIKO’s recommendations target specific high-risk groups, including men who have sex with men and frequently change sexual partners, as well as laboratory personnel handling infectious Mpox samples. The standard immunization schedule comprises two vaccine doses.
Study Methodology: Rigorous Evaluation
The Charité study was strategically designed with two distinct arms to comprehensively evaluate the Mpox vaccine. The safety and tolerability arm involved prospective examination and regular surveys of approximately 6,500 individuals. The effectiveness arm employed a rolling cohort design, simulating a randomized clinical trial through a retrospective comparison of data from over 9,300 vaccinated and unvaccinated subjects with comparable demographic and clinical profiles. Across all participants, irrespective of HIV status, the study determined an overall vaccine effectiveness of 58%. This extensive research was jointly funded by the BIH and the EMA, underscoring the collaborative effort to understand and combat the Mpox epidemic.