Marburg virus disease (MVD) is a severe and often fatal illness, posing a significant global health threat. Its unpredictable outbreaks and high fatality rates underscore the urgent need for effective preventive measures. Developing a safe and efficacious vaccine is a high priority to combat this dangerous pathogen and protect vulnerable populations worldwide.
Understanding Marburg Virus
The Marburg virus, a member of the Filoviridae family alongside Ebola, was first identified in 1967 following outbreaks in Marburg and Frankfurt, Germany, and Belgrade, Serbia, linked to African green monkeys imported from Uganda. This virus is primarily transmitted to humans from Rousettus fruit bats, considered its natural reservoir. Human-to-human transmission occurs through direct contact with bodily fluids of infected individuals, or with contaminated surfaces and materials.
The incubation period for MVD ranges from 2 to 21 days, though symptoms typically appear within 5 to 10 days. The disease begins abruptly with a high fever, severe headache, and muscle aches. As the illness progresses, patients may experience severe watery diarrhea, abdominal pain, nausea, and vomiting.
Around the fifth day, a maculopapular rash may appear. In severe cases, MVD can lead to hemorrhagic manifestations, including bleeding from the nose, gums, and internal organs, as well as multi-organ dysfunction and shock. The case fatality rate for MVD is notably high, ranging from 23% to 90% in past outbreaks.
Current Vaccine Approaches and Progress
The global scientific community is actively pursuing various vaccine platforms for Marburg virus, with at least 28 candidates in different stages of development. The World Health Organization (WHO) has prioritized four of these candidates for evaluation in human trials, based on their safety, immunogenicity, potential efficacy, and availability for deployment. All four prioritized candidates are viral vector vaccines, which use a modified, harmless virus to deliver genetic instructions for a Marburg virus protein into human cells.
One leading candidate is an adenovirus-based vaccine developed by the Sabin Vaccine Institute. This vaccine has completed a Phase 1 trial, demonstrating safety and robust immune responses in 40 adults, and is currently undergoing a Phase 2 trial in 125 adults in Uganda and Kenya. Another adenovirus-based vaccine, developed at the University of Oxford, utilizes the same ChAdOx1 platform as their COVID-19 vaccine and began a Phase 1 trial in the UK earlier this year.
Two other promising candidates, developed by the International AIDS Vaccine Initiative (IAVI) and Public Health Vaccines LLC, use a vesicular stomatitis virus (VSV) vector to deliver the genetic code for a Marburg virus protein. This VSV platform is also the basis for the licensed Ebola vaccine, Ervebo, which is effective against the Zaire ebolavirus. These VSV-based vaccines have shown full protection in non-human primate models, even at significantly reduced doses, and offer rapid onset of protection after a single dose.
How Marburg Vaccines Function
Marburg virus vaccines are designed to train the human immune system to recognize and neutralize the virus before it can cause widespread infection. A key component targeted by these vaccines is the Marburg virus glycoprotein (GP). This protein is located on the exterior of the viral particle and is essential for the virus to bind to and enter host cells. By introducing genetic information or a modified form of this glycoprotein, vaccines prompt the body to produce antibodies against it.
When a vaccinated individual is exposed to Marburg virus, the immune system, having been “trained” by the vaccine, can quickly identify the glycoprotein. Antibodies produced in response to the vaccine can bind to the viral glycoprotein, preventing the virus from entering host cells. Some antibodies may also recruit immune cells to destroy infected cells. In addition to antibody responses, vaccines can also stimulate T-cell responses, which are another arm of the immune system capable of directly killing infected cells. The goal is to induce a strong and durable immune response that provides protective immunity.
Vaccine Deployment Strategies
Once a Marburg virus vaccine receives approval, its effective deployment will be crucial for controlling outbreaks. Several strategies are being considered to maximize vaccine impact, particularly given the sporadic and often remote nature of Marburg outbreaks. One strategy is ring vaccination, which involves vaccinating the immediate contacts of confirmed cases, as well as the contacts of those contacts. This approach aims to create a “ring” of immunity around an infected individual, thereby limiting further transmission.
Targeted vaccination of high-risk groups represents another important strategy. This includes vaccinating healthcare workers at elevated risk of exposure. Individuals living near or working in mines or caves, which are known habitats for Rousettus fruit bats and potential sources of initial human infection, may also be prioritized for prophylactic vaccination. Strategic stockpiling of vaccine doses would allow for rapid deployment in the event of an outbreak, ensuring that sufficient supplies are available to implement these strategies swiftly. Logistical challenges, such as maintaining cold chains for vaccine storage and transportation in remote areas with limited infrastructure, will require careful planning and resources to ensure successful and equitable distribution.