Research Advances Towards a Vaccine for Filoviruses, Including Ebola

Filoviruses, a family of highly pathogenic viruses, pose significant threats to public health worldwide. The most notorious members of this group are the Ebola and Marburg viruses, both of which are known for their severe hemorrhagic fevers and high mortality rates. Despite decades of study, much remains unknown about these viruses, which primarily transfer from animals to humans, often through practices like hunting and butchering bushmeat.

Currently, there are only two approved vaccines that specifically target Ebola virus infection. In an effort to expand protective measures against other filoviruses, a multidisciplinary team at a U.S. military research facility has undertaken research to assess whether existing Ebola vaccines can also provide immunity to other members of the filovirus family.

Simultaneously, researchers at the University of Texas Medical Branch in Galveston are testing a promising antiviral pill, obeldesivir, which has shown potential in treating Rhesus macaques infected with the Ebola virus. This medication is an oral counterpart to Remdesivir, a treatment initially developed for COVID-19.

The military researchers conducted extensive experiments to explore the efficacy of a recombinant Ebola vaccine that incorporates elements from various filoviruses. Although the results did not meet their initial expectations, the research has contributed to a deeper understanding of the requirements for developing a multivalent vaccine capable of providing protection against multiple filoviruses. The findings were published in the journal Science Translational Medicine.

Filoviruses like Ebola and Marburg are classified as negative-sense single-strand RNA viruses, which are associated with severe disease outbreaks. The mortality rates for Marburg virus outbreaks in Africa have ranged from 83% to 88%, highlighting the urgent need for effective vaccines.

The Marburg virus was first identified in 1967 following infections among laboratory personnel in Europe, who had been exposed to green monkeys imported from Uganda. This incident marked the beginning of our awareness of filoviruses, which have only recently been addressed in terms of vaccine development.

While the Ebola virus first emerged in a documented outbreak in 1976, with a death toll of around 280 individuals, the need for vaccines has become increasingly urgent following significant outbreaks in the last few decades. The outbreak in West Africa from 2014 to 2016 spurred advancements in vaccine development, leading to the approval of the Ervebo vaccine by the U.S. Food and Drug Administration and the European Medicines Agency in 2019.

In their investigation, the researchers focused on a second Ebola vaccine developed by Janssen Pharmaceuticals, which operates under Johnson & Johnson. This vaccine requires a two-part regimen: an initial dose followed by a booster, designed to be administered several weeks apart. The first dose utilizes an adenovirus vector to deliver the genetic material coding for the Ebola virus's glycoprotein, while the second dose employs a modified vaccinia Ankara vector that encodes glycoproteins from multiple filoviruses.

The study involved 583 volunteers from various countries, including the United States and several African nations. Participants were split into two groups to assess the effectiveness of the vaccine regimen and to explore the immune response to multiple filovirus components.

Blood tests revealed that while the vaccine elicited a strong immune response against the Ebola virus, it did not demonstrate substantial reactivity against other filoviruses. This raised concerns regarding the vaccine's broader applicability. Additionally, blood samples from survivors of a Bundibugyo virus outbreak indicated limited cross-reactivity, further emphasizing the challenge of developing a comprehensive vaccine.

These findings underscore the need for multivalent vaccines that could offer broader protection against various filoviruses, a crucial step in enhancing global health security against these deadly pathogens.