A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection

Bibliographic Details
Title: A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection
Authors: Adam J. Ronk, Nicole M. Lloyd, Min Zhang, Caroline Atyeo, Hailee R. Perrett, Chad E. Mire, Kathryn M. Hastie, Rogier W. Sanders, Philip J. M. Brouwer, Erica Olmann Saphire, Andrew B. Ward, Thomas G. Ksiazek, Juan Carlos Alvarez Moreno, Harshwardhan M. Thaker, Galit Alter, Sunny Himansu, Andrea Carfi, Alexander Bukreyev
Source: Nature Communications, Vol 14, Iss 1, Pp 1-13 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-41376-6
Access URL: https://doaj.org/article/4afd193033d54672afc7fc5b00f7b333
Accession Number: edsdoj.4afd193033d54672afc7fc5b00f7b333
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-41376-6
Published in:Nature Communications
Language:English