A novel strategy for developing live-attenuated arenavirus vaccines.
Problem Solved by the Technology
Arenaviruses have a significant impact on public health and pose a credible threat to biodefense.There are four arenaviruses that cause severe hemorrhagic fever in humans (Lassa virus, endemic to Africa; and Machupo, Junin, and Guanarito viruses endemic to South America). A fifth arenavirus, lymphocytic choriomeningitis virus (LCMV), is found throughout the world and it is particularly troublesome for immunocompromised individuals. Safe and effective arenavirus vaccines have remained elusive and none are currently available. Therapy is limited to off-label use of ribavirin, which is only partially effective and carries many undesired side-effects.
Researchers at the University of Rochester are developing a codon deoptimization (CD) -based approach as a novel strategy for live-attenuated arenavirus vaccines.
This approach is based on recoding certain proteins of the virus with least frequently used codons in mammalian cells. Research has shown that a recoded LCMV is genetically and phenotypically stable during serial passages in FDA vaccine development-approved Vero cells. In vivo experiments in a LCMV-infected mouse model have shown that the recoded viruses were highly attenuated and conferred complete protection against a subsequent lethal challenge with wild-type LCMV.
These results indicate the safety, efficacy, and stability of this CD-based approach for developing live-attenuated vaccine candidates against human pathogenic arenaviruses.
1. Cheng BY et al. "Development of live-attenuated arenavirus vaccines based on codon deoptimization," J Virol. 2015 Apr 1;89(7):3523-33. PMID: 25589652
2. Ortiz-Riaño E et al. "Arenavirus reverse genetics for vaccine development," J Gen Virol. 2013 Jun;94(Pt 6):1175-88. PMID: 23364194
3. Cheng BY et al. “Generation of recombinant arenavirus for vaccine development in FDA-approved Vero cells,” J Vis Exp. 2013 Aug 1;(78). PMID: 23928556