PRECLINICAL DEVELOPMENT OF A CHIMERIC YELLOW FEVER / TICK-BORNE ENCEPHALITIS VIRUS AS A CANDIDATE VACCINE
Main Article Content
Authors
T. Kulatay
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
E. Sedova
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
A. Shevtsov
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
G. Zauatbayeva
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
B. Ingirbay
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
V. Keyer
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
Zh. Shakhmanova
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
M. Zhumabekova
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
Ye. Abduraimov
National Holding QazBioPharm, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
A. Rsaliyev
National Holding QazBioPharm, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
N. Sikhayeva
National Holding QazBioPharm, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
I. Kozlova
Federal State Budgetary Scientific Institution «Scientific Сentre for Family Health and Human
A. Shustov
National Center for Biotechnology, Astana, Kazakhstan, 13/5, Kurgalzhyn road, 010000
Abstract
Tick-borne encephalitis virus (TBEV) is a reemerging pathogen in Kazakhstan. Despite the availability of inactivated TBEV vaccines produced abroad, their reliance on complex multi-dose regimens and frequent boosters limits their implementation for routine use in Kazakhstan. New technologies, including chimerization of different Flavivirus species, enable the development of vaccine candidates which require only a single dose to achieve long-lasting immunity. The ChimeriVax platform leverages the efficient replication machinery of the yellow fever virus (YFV) 17D vaccine strain engineered to express the structural proteins of a different flavivirus.
In this work, the ChimeriVax YFV/TBEV virus was created by replacing the prM-E genes in the YFV genome with the prM-E genes of TBEV. Preclinical evaluation demonstrated robust replication (~10^8 focus-forming units, FFU/mL) in cell cultures and genetic stability over multiple passages. In murine models, the chimeric virus elicited transient viremia (peaking at 10^4 FFU/mL) without mortality even at high doses (10^5 FFU). Immunization induced potent neutralizing antibodies (geometric mean titer: 4,076) and robust cellular immunity, marked by production of the cytokines IFN-γ, TNF-α, and IL-2 upon antigen stimulation. These results position the ChimeriVax YFV/TBEV virus as a promising vaccine candidate.
Keywords
live-attenuated vaccine, chimeric flavivirus vaccine, Tick-borne encephalitis virus, neutralizing antibodies, cellular immunity, preclinical development
Article Details
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