A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection
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 Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 12, 2023
- Source ID
- 10.1038/s41467-023-41376-6
Entities
People
- Adam J Ronk
- Alexander Bukreyev
- Andrea Carfì
- Andrew B Ward
- Caroline Atyeo
- Chad E Mire
- Erica Ollmann Saphire
- Galit Alter
- Hailee R. Perrett
- Harshwardhan M. Thaker
- Juan Carlos Alvarez Moreno
- Kathryn M Hastie
- Min Zhang
- Nicole Lloyd
- Philip J. M. Brouwer
- Rogier W Sanders
- Sunny Himansu
- Thomas G. Ksiazek
Organizations
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense