Article ; Online: Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates.
Emerging microbes & infections
2024 Volume 13, Issue 1, Page(s) 2301061
Abstract: Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) ...
| Abstract | Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the |
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| MeSH term(s) | Humans ; Animals ; Lassa virus ; Lassa Fever ; Virulence ; Macaca fascicularis ; Antibodies, Monoclonal/pharmacology |
| Chemical Substances | Antibodies, Monoclonal |
| Language | English |
| Publishing date | 2024-01-22 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2681359-2 |
| ISSN | 2222-1751 ; 2222-1751 |
| ISSN (online) | 2222-1751 |
| ISSN | 2222-1751 |
| DOI | 10.1080/22221751.2023.2301061 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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