Progress in recombinant DNA-derived vaccines for Lassa virus and filoviruses.

Developing vaccines for highly pathogenic viruses such as those causing Lassa, Ebola, and Marburg hemorrhagic fevers is a daunting task due to both scientific and logistical constraints. Scientific hurdles to overcome include poorly defined relationships between pathogenicity and protective immune responses, genetic diversity of viruses, and safety in a target population that includes a large number of individuals with compromised immune systems. Logistical obstacles include the requirement for biosafety level-4 containment to study the authentic viruses, the poor public health infrastructure of the endemic disease areas, and the cost of developing these vaccines for use in non-lucrative markets. Recombinant DNA-based vaccine approaches offer promise of overcoming some of these issues. In this review, we consider the status of various recombinant DNA candidate vaccines against Lassa virus and filoviruses which have been tested in animals.

Grant-Klein RJ ，Altamura LA ，Schmaljohn CS 《-》

Progress in filovirus vaccine development: evaluating the potential for clinical use.

Falzarano D ，Geisbert TW ，Feldmann H 《-》

Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses.

Marzi A ，Feldmann F ，Geisbert TW ，Feldmann H ，Safronetz D ... -  《-》

DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs.

Cashman KA ，Wilkinson ER ，Wollen SE ，Shamblin JD ，Zelko JM ，Bearss JJ ，Zeng X ，Broderick KE ，Schmaljohn CS ... -  《-》

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

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.

Flaxman A ，Sebastian S ，Appelberg S ，Cha KM ，Ulaszewska M ，Purushotham J ，Gilbride C ，Sharpe H ，Spencer AJ ，Bibi S ，Wright D ，Schmidt I ，Dowall S ，Easterbrook L ，Findlay-Wilson S ，Gilbert S ，Mirazimi A ，Lambe T ... -  《-》