A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

Autor: Kevin Tierney, David Safronetz, Geoff Soule, Bryce M. Warner, Kathy L. Frost, Stephanie A. Booth, Derek R. Stein
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: npj Vaccines, Vol 4, Iss 1, Pp 1-7 (2019)
NPJ Vaccines
ISSN: 2059-0105
Popis: The World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates.
Lassa virus: Recombinant VSV Lassa virus vaccine Lassa virus (LASV) is an emerging pathogen that can be associated with high case fatality but for which no clinically-approved vaccine currently exists. David Safronetz and colleagues at the Public Health Agency of Canada and the University of Manitoba investigate the efficacy of a single dose of a recombinant vaccine of LASV glycoproteins vectorized into vesicular stomatitis virus (VSVΔG/LASVGPC). Using guinea pigs lethally challenged with LASV, the protective efficacy of VSVΔG/LASVGPC and LASV-specific IgG is assessed at a number of time points out to approximately one year after vaccination. VSVΔG/LASVGPC elicits stable LASV glycoprotein-specific antibody production and durable protection from lethal LASV challenge, with 71% of animals surviving even at one year following vaccination and complete protection being afforded at earlier (weeks) time points. This pre-clinical model demonstrates the stable protection that can be established by a single dose of VSVΔG/LASVGPC.
Databáze: OpenAIRE
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