[Source: Journal of Virology, full page: (LINK). Abstract, edited.]
Chikungunya virus vaccine candidates with decreased mutational robustness are attenuated in vivo and have compromised transmissibility.
Lucía Carrau, Veronica V. Rezelj, María G. Noval, Laura I. Levi, Daniela Megrian, Herve Blanc, James Weger-Lucarelli, Gonzalo Moratorio, Kenneth Stapleford, Marco Vignuzzi
Chikungunya virus (CHIKV) is a re-emerged arbovirus, member of the Togaviridae family. It circulates through mosquito vectors mainly of the Aedes family and a mammalian host. CHIKV causes chikungunya fever, a mild to severe disease characterized by arthralgia, with some fatal outcomes described. In the past years, several outbreaks mainly caused by enhanced adaptation of the virus to the vector and ineffective control of the contacts between infected mosquito populations and the human host have been reported. Vaccines represent the best solution for the control of insect-borne viruses, including CHIKV, but are often unavailable. We designed live attenuated CHIKV by applying a rational genomic design based on multiple replacements of synonymous codons. In doing so, the virus mutational robustness (capacity to maintain phenotype despite introduction of mutations to genotype) is decreased, driving the viral population towards deleterious evolutionary trajectories. When tested in the insect and mammalian hosts, we observed overall strong attenuation in both and greatly diminished signs of disease. Moreover, we found the vaccine candidates elicited protective immunity, related to the production of neutralizing antibodies after a single dose. During an experimental transmission cycle between mosquitoes and naïve mice, vaccine candidates could be transmitted by mosquito bite leading to asymptomatic infection in mice with compromised dissemination. Using deep sequencing technology we observed an increase in detrimental (stop) codons, which confirmed the effectiveness of this genomic design. Because the approach involves hundreds of synonymous modifications to the genome, the reversion risk is significantly reduced, rendering them promising vaccine candidates.
Chikungunya fever is a debilitating disease that causes severe pain to the joints, which can compromise the patient’s lifestyle for several months and even in some grave cases lead to death. The etiological agent is chikungunya virus, an alphavirus transmitted by mosquito bite. Currently there are no approved vaccines or treatments against the disease. In our research, we developed novel live attenuated vaccine candidates against chikungunya virus by applying an innovative genomic design. When tested in the insect and mammalian host, the vaccine candidates did not cause disease, elicited strong protection against further infection and had low risk of reversion to pathogenic phenotypes.
Copyright © 2019 Carrau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Alphavirus; Togavirus; Chikungunya fever; Vaccines.