Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate

PLoS Neglected Tropical Diseases
Kenneth S PlanteScott Weaver

Abstract

We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footp...Continue Reading

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Citations

Feb 9, 2016·Virology·Rachmat HidajatPeter Pushko
Apr 8, 2016·Expert Review of Vaccines·Peter PushkoIrina Tretyakova
Mar 30, 2016·The American Journal of Tropical Medicine and Hygiene·Shannan L RossiScott C Weaver
May 7, 2016·PLoS Neglected Tropical Diseases·Stuart D DowallRoger Hewson
Aug 29, 2018·Molecular Systems Biology·Daniela MichlmayrEva Harris
Dec 4, 2019·The Journal of Clinical Investigation·Anthony J LentscherTerence S Dermody
Aug 30, 2019·Journal of Virology·Bryan A JohnsonVineet D Menachery
Mar 2, 2017·The Journal of Clinical Investigation·Laurie A Silva, Terence S Dermody
May 7, 2016·PLoS Neglected Tropical Diseases·M Javad Aman, Fatah Kashanchi
Dec 7, 2016·The Journal of Infectious Diseases·Katrin Ramsauer, Frédéric Tangy
Jan 11, 2020·Frontiers in Microbiology·Shan GaoLeiliang Zhang
Jan 18, 2019·PLoS Neglected Tropical Diseases·Giovanni Rezza, Scott C Weaver
Dec 7, 2016·The Journal of Infectious Diseases·Jesse H ErasmusScott C Weaver
Oct 22, 2020·NPJ Vaccines·Christopher M WeissLark L Coffey
Feb 17, 2021·Virus Genes·Friederike I L HuckeJoachim J Bugert
Jun 24, 2016·Microbiology Spectrum·Clayton R MorrisonMark T Heise
Jun 1, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Emily A VoigtNeal Van Hoeven

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Methods Mentioned

BETA
in vitro transcription
amplicon sequencing

Software Mentioned

PyMol Graphics System
Pymol
LivingImage

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