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Immunogenicity and protection of a triple repeat domain III mRNA vaccine against Zika virus

Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the deve...

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Published in:Vaccine 2025-01, Vol.43 (Pt 2), p.126518, Article 126518
Main Authors: Lee, Yu-Sun, Cheong, Mi Sun, Lee, Jisun, Bang, Eun-Kyoung, Park, Sang In, Park, Hyo-Jung, Bae, Seo-Hyeon, Yoon, Subin, Roh, Gahyun, Lee, Seonghyun, Cho, Youngran, Ha, Dahyeon, Oh, Ayoung, Lee, Soo-Yeon, Choi, Eun-Jin, Choi, Huijeong, Jo, Sohee, Lee, Yeeun, Kim, Jungmin, Kwak, Hye Won, Bang, Yoo-Jin, Lee, Dabin, Shim, Heeyoun, Park, Young Kun, Keum, Gyochang, Nam, Jae-Hwan, Kim, Wonil
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Language:English
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Summary:Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the development of ZIKV vaccine using DNA and RNA as well as recombinant protein technologies; however, the outcomes thus far have not been consistently noteworthy. In this study, we designed an mRNA vaccine for ZIKV and evaluated its immunogenicity using a mouse model. Our vaccine, termed 3xEIII, encodes a triple repeat of domain III from the ZIKV E protein. We effectively encapsulated the mRNA within lipid nanoparticles (LNPs), administered 3xEIII to mice via two intramuscular injections, and assessed the induced humoral and cellular immune responses. Specifically, the vaccine elicited neutralizing antibodies that effectively eliminated ZIKV from the organs of challenged mice. Notably, 3xEIII conferred both protective effects and long-term immunity. In subsequent challenges conducted 40 weeks after boosting, immunized mice experienced temporary weight loss but showed significantly reduced viral titers in target organs by the 9th day post-infection. Conclusively from these findings, 3xEIII stands out as a promising noteworthy mRNA vaccine candidate for Zika virus. •The vaccine targets domain III of the ZIKV E protein essential for virus entry.•The ZIKV mRNA vaccine effectively induces neutralizing antibody responses in mice.•The vaccine activates T and B cell responses to promote cellular and humoral immunity.•Long-term immunity is evident with lower viral titers in organs after the boost.
ISSN:0264-410X
1873-2518
1873-2518
DOI:10.1016/j.vaccine.2024.126518