By Hendra Lukman 
A groundbreaking study conducted at Charité – Universitätsmedizin Berlin has provided crucial insights into the effectiveness of the Imvanex vaccine against Mpox, revealing an overall protection rate of 84% after a single dose for individuals without HIV. However, the research also underscores a significant vulnerability: a single dose offers insufficient protection for people living with HIV, even those on effective antiretroviral therapy. These findings, published in the prestigious journal The Lancet Infectious Diseases, emphasize the urgent need for all at-risk groups, and particularly individuals with HIV, to adhere to the recommended two-dose vaccination regimen.
A Global Health Concern and the Role of Imvanex
The emergence of a widespread Mpox outbreak in 2022 propelled the virus onto the global health stage, prompting swift action from public health authorities. In Germany, the Standing Commission on Vaccination (STIKO) issued recommendations for Imvanex vaccination among individuals at elevated risk of infection. Imvanex, originally developed to combat smallpox, received approval from the European Medicines Agency (EMA) for Mpox protection in July 2022, responding to the escalating public health emergency. This approval was predicated on laboratory data suggesting cross-protective capabilities against the Mpox virus, a close relative of the eradicated smallpox virus (Variola major). While the EMA’s decision was based on this scientific evidence, the precise extent of this protective effect, particularly within vulnerable populations, remained a critical question demanding further investigation.
Comprehensive Study Design and Key Findings
To address this knowledge gap, the EMA commissioned a large-scale, comprehensive 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 study marked a significant advancement by being the first to directly compare vaccine effectiveness between individuals with and without HIV.
"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 research effort involved over 9,300 participants, primarily men and trans individuals who reported having sex with men or trans individuals. This demographic aligns with the groups for whom STIKO recommends vaccination. The study, conducted from July 2022 to December 2023, employed a robust design: half of the participants received a single dose of the Imvanex vaccine, while the other half remained unvaccinated. Both groups were then monitored for an average of two months to meticulously track the incidence of Mpox infections.
Differential Protection: HIV-Negative vs. HIV-Positive Individuals
The results for HIV-negative participants were highly encouraging. A significantly lower number of Mpox cases were observed in the vaccinated group compared to the unvaccinated cohort, demonstrating an impressive 84% vaccine effectiveness. Professor Sander expressed optimism about this figure, noting, "That is a very good figure, which is likely increased even further by the second vaccine dose." While the study could not definitively quantify the additional benefit of a second dose due to a notable decline in infections in the latter half of 2022, the initial single-dose effectiveness for this group was substantial.
In stark contrast, the study identified only a minimal, statistically insignificant protective effect of a single vaccine dose in individuals living with HIV. Professor Sander elaborated on the underlying immunological mechanisms: "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 suggests that a single dose may not be sufficient to elicit a robust and sustained immune response in individuals with compromised immune systems, even when well-managed.
The Imperative of a Two-Dose Regimen
Professor Florian Kurth, Head of the Clinical Infection Research Group at Charité and a leading figure in the study alongside Professor Sander, strongly emphasized the critical importance of completing the full vaccination course. "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 stated. He extended this recommendation to all other at-risk groups, underscoring that a two-dose regimen typically leads to more durable and comprehensive immune protection. Future research is planned to precisely delineate the long-term protective benefits conferred by two doses across different demographic groups.
Milder Symptoms and Reduced Transmission Risk
Beyond infection prevention, the study also shed light on the vaccine’s impact on symptom severity. Vaccinated participants who contracted Mpox generally experienced milder illness. They exhibited fewer pox lesions, which healed more rapidly, and reported a lower incidence of systemic symptoms such as fever. Professor Kurth posited, "We assume that the second vaccination further reduces the manifestation of such symptoms. Fewer pox lesions presumably also reduces the risk of transmitting the virus. Full vaccination should therefore ward off Mpox outbreaks." This suggests that even if breakthrough infections occur, a fully vaccinated individual may be less contagious and experience a less debilitating illness.
Vaccine Tolerability and Safety Profile
The research team also conducted a thorough assessment of the Imvanex vaccine’s tolerability and safety, examining data from 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. He also reiterated the importance of understanding that full immune protection develops approximately 14 days post-vaccination and advised continued adherence to general preventive measures, such as condom use, which also protects against other sexually transmitted infections.
Relevance to Current and Future Outbreaks
The study’s findings are directly applicable to clade IIb of the Mpox virus, the strain that circulated in Germany during the study period. Crucially, clade IIb shares a close genetic relationship with clade I, which is currently prevalent in Central Africa and surrounding regions. This genetic similarity leads the researchers to anticipate a high degree of cross-protection, suggesting that the study’s conclusions may also hold significant relevance for understanding and combating the ongoing clade I outbreak in Africa. However, questions regarding the long-term duration of vaccine-induced immunity remain. The research team plans to address these by initiating long-term follow-up studies and investigating the potential benefits of a third vaccine dose.
Understanding Mpox: A Public Health Perspective
Mpox, formerly known as monkeypox, is a viral illness caused by the monkeypox virus, a member of the Poxviridae family, closely related to the virus that caused smallpox. While eradicated in 1980, smallpox was a historically devastating disease. Mpox generally presents with a milder clinical course than smallpox. Typical symptoms include fever, headache, muscle aches, back pain, and swollen lymph nodes. A characteristic rash, often described as pustules, appears a few days later and can be intensely itchy and painful. While Mpox-related fatalities are rare, they are more commonly observed in children and immunocompromised individuals. Severe cases can lead to significant scarring and long-term health consequences. Transmission occurs through close physical contact.
Global Infection Trends and Public Health Responses
The Mpox virus is classified into clades based on genetic variations. The global outbreak of clade IIb, which began in May 2022, primarily spread through close and sexual contact, leading to over 100,000 recorded cases across 122 countries. While infection rates in Europe saw a considerable decline following the autumn of 2022, some nations, including the USA, Brazil, and Argentina, have reported over 1,000 cases in 2024. New clade IIb cases have also emerged in Australia, South Africa, and South America. Concurrently, an increasing number of clade I Mpox infections, including a new Ib variant, have been documented in Africa since 2023, particularly in the Democratic Republic of the Congo. In response to the growing global threat, the World Health Organization (WHO) declared the clade II outbreak a Public Health Emergency of International Concern (PHEIC) in 2022, followed by a similar declaration for the clade I outbreak in 2024.
The Imvanex Vaccine: A Key Tool in Prevention
Germany’s STIKO recommends Imvanex, an EMA-approved vaccine, for Mpox prevention. Initially approved for smallpox in 2013, its use for Mpox was authorized in July 2022. The vaccine is also available in the USA and Canada under different brand names, Jynneos and Imvamune, for several years. Imvanex is a live-attenuated vaccine, meaning it contains a weakened virus incapable of replicating in the human body. It is based on a modified Vaccinia virus Ankara (MVA), which acts as a prototype pox virus, thereby inducing cross-protection against other pox viruses. The current recommendation for basic immunization involves a two-dose schedule, targeting individuals at higher risk, including men aged 18 and over who have sex with men and engage in frequent partner changes, as well as laboratory personnel working with infectious Mpox samples.
Study Methodology and Funding
The Charité study was structured into two distinct arms to comprehensively evaluate both the safety and effectiveness of the Imvanex 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 within an emulated target trial framework. By retrospectively comparing data from over 9,300 vaccinated and unvaccinated subjects with similar demographic and clinical profiles, researchers effectively simulated a randomized clinical trial. Across all participants, irrespective of HIV status, the vaccine demonstrated an average effectiveness of 58%. This critical research initiative was supported by funding from the BIH and the EMA, underscoring the collaborative effort to address this significant public health challenge.