Construction and Immunological Evaluation of an Adenoviral Vector-Based Vaccine Candidate for Lassa Fever
Open Access
- 15 March 2021
- Vol. 13 (3), 484
- https://doi.org/10.3390/v13030484
Abstract
Lassa virus (LASV) is a rodent-borne arenavirus circulating in West African regions that causes Lassa fever (LF). LF is normally asymptomatic at the initial infection stage, but can progress to severe disease with multiorgan collapse and hemorrhagic fever. To date, the therapeutic choices are limited, and there is no approved vaccine for avoiding LASV infection. Adenoviral vector-based vaccines represent an effective countermeasure against LASV because of their safety and adequate immunogenicity, as demonstrated in use against other emerging viral infections. Here, we constructed and characterized a novel Ad5 (E1-, E3-) vectored vaccine containing the glycoprotein precursor (GPC) of LASV. Ad5-GPCLASV elicited both humoral and cellular immune responses in BALB/c mice. Moreover, a bioluminescent imaging-based BALB/c mouse model infected with GPC-bearing and luciferase-expressing replication-incompetent LASV pseudovirus was utilized to evaluate the vaccine efficacy. The bioluminescence intensity of immunized mice was significantly lower than that of control mice after being inoculated with LASV pseudovirus. This study suggests that Ad5-GPCLASV represents a potential vaccine candidate against LF.Keywords
Funding Information
- National Major Science and Technology Projects of China (2016ZX10004001)
This publication has 41 references indexed in Scilit:
- Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunitsNature Communications, 2016
- Inhibition of Innate Immune Responses Is Key to Pathogenesis by ArenavirusesJournal of Virology, 2016
- Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trialThe Lancet, 2015
- Building Phylogenetic Trees from Molecular Data with MEGAMolecular Biology and Evolution, 2013
- Envelope Glycoprotein of ArenavirusesViruses, 2012
- T Cell-Dependence of Lassa Fever PathogenesisPLoS Pathogens, 2010
- Overcoming pre-existing adenovirus immunity by genetic engineering of adenovirus-based vectorsExpert Opinion on Biological Therapy, 2009
- Inactivated Lassa virus elicits a non protective immune response in rhesus monkeysJournal of Medical Virology, 1992
- The rapid generation of mutation data matrices from protein sequencesBioinformatics, 1992
- Clinical Virology of Lassa Fever in Hospitalized PatientsThe Journal of Infectious Diseases, 1987