LY-CoV555, a SARS-CoV-2 spike protein–specific antibody, neutralizes SARS-CoV-2 and protects the airways of nonhuman primates against infection.

Ebola-virus-targeting short interfering RNAs (siRNAs) encapsulated in lipid nanoparticles are adapted to the current outbreak strain of the virus, and the siRNA cocktail is shown to protect nonhuman primates fully when administered 3 days after challenge with the current West African Ebola virus isolate; upon viral sequence data availability, the drug can be adapted to the new virus and produced in as little as 8 weeks. Ebola virus-targeting siRNAs encapsulated in lipid nanoparticles (TKM-Ebola) have been shown previously to provide post-exposure protection of nonhuman primates against lethal Ebola virus challenge. The therapy has also been used on compassionate grounds in a number of human patients in the current outbreak, although the efficacy in humans is not known. Here, Thomas Geisbert and colleagues rapidly adapt the TKM-Ebola cocktail to the current outbreak strain of the virus and show that it is able to fully protect nonhuman primates when administered 3 days after challenge with the current West African EBOV isolate. Once viral sequence data becomes available, the drug can be adapted to the new virus and produced in as little as 8 weeks. The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled1. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States2. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.

Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiV_M) and Bangladesh (NiV_B). Differences in transmission patterns and mortality rates suggest that NiV_B may be more pathogenic than NiV_M. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiV_M and 4 AGMs were exposed to NiV_B. While NiV_B was uniformly lethal, only 50% of NiV_M-infected animals succumbed to infection. Histopathology of lungs and spleens from NiV_B-infected AGMs was significantly more severe than NiV_M-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiV_M infection, was much shorter in NiV_B-infected AGMs. Together, these data show that NiV_B is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy.

A monoclonal antibody against Nipah virus has in vivo efficacy in a nonhuman primate.

The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions.