Potent immunogenicity and protective efficacy of a multi-pathogen vaccination targeting Ebola, Sudan, Marburg and Lassa viruse

• Published in: PLoS pathogens 2024-06, Vol.20 (6), p.e1012262
• Main Authors: Flaxman, Amy, Sebastian, Sarah, Appelberg, Sofia, Cha, Kuan M, Ulaszewska, Marta, Purushotham, Jyothi, Gilbride, Ciaran, Sharpe, Hannah, Spencer, Alexandra J, Bibi, Sagida, Wright, Daniel, Schmidt, Isabel, Dowall, Stuart, Easterbrook, Linda, Findlay-Wilson, Stephen, Gilbert, Sarah, Mirazimi, Ali, Lambe, Teresa
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animal models; Antibodies; Antigens; Biology and life sciences; Cell-mediated immunity; Chemokines; Disease prevention; Ebola virus; Ebola virus infections; Ebolavirus; Epidemics; Ethics; Fatalities; Fever; Humoral immunity; Immunogenicity; Infectious diseases; Inventors; Lassa fever; Marburg disease; Marburg virus disease; Medicine and Health Sciences; Morbidity; Outbreaks; Pathogens; Pharmaceutical research; Prevention; Proteins; Public health; Research and Analysis Methods; Severe acute respiratory syndrome coronavirus 2; Vaccine development; Vaccines; Vaccinia; Vectors (Biology); Viral diseases; Viral vaccines; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012262

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.