Optimization of Zika virus for vaccine development through the enhancement of innate immune activation 3499
Year: 2025
Type: article
Abstract: Description The Zika virus (ZIKV), first identified in 1947, did not cause wide-spread outbreaks until 2015, with no large-scale epidemics reported since 2017. Whole-genome sequencing of virus strains from the pre-epidemic, epidemic, and post-epidemic periods identified a V188A mutation in the NS1 protein, associated with host IFN response regulation, suggesting ZIKV virulence has co-evolved with host immune systems. Our previous experiment in which Balb/c mice were immunized with an adjuvanted, inactivated 2006 ZIKV isolate elicited a poor neutralizing antibody response. Subsequent genome sequencing revealed the V188A mutation in the NS1of the isolate. These results showing that the potentially linked to an increased susceptibility to IFN responses and the presence of additional regulatory elements in Zika virus strains indicates a need for further purification. Through serial Vero cell passages and plaque purification, we isolated a high-titer, plaque-purified virus clone that elicited stronger neutralizing antibody responses and enhanced protective effects in Balb/c mice. Moreover, intravenous infection with the plaque-purified virus induced significant immune cell recruitment and cytokine production in lymphoid tissues compared to the unpurified parental clones. Future studies will explore the mechanisms driving interactions between purified viral clones and host cells, particularly focusing on innate immune activation, including IFN responses for optimizing vaccine efficacy. Topic Categories Vaccines and Immunotherapy (VAC)
Source: The Journal of Immunology
Authors: Tzu-Ting Lin, Wei-Yu Chen, Chia Chi Ku
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: European Commission, Helse Sør-Øst RHF
OpenAlex ID: W4416449796
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