Advanced science (Weinheim, Baden-Wurttemberg, Germany)Dec 26, 2025

Strong and Lasting Immune Response from Lipid Nanoparticle mRNA Vaccine Against Shingles Developed Using AI

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 7, 2026

Abstract

The novel mRNA-LNP vaccine targeting VZV glycoprotein E elicits strong immune responses and shows potential for effective herpes zoster prevention.

AI-based screening identified promising vaccine candidates from numerous antigen sequences.
The vaccine VZV-gEmD produced significant levels of gE-specific IgG antibodies and VZV-specific antibodies in rhesus macaques.
CD4 T-cell responses associated with the vaccine were significantly stronger and longer lasting than those observed with Shingrix.
The study explored the relationship between the cellular localization of vaccine components and their ability to provoke immune responses.
A 4-week administration interval was validated for its effectiveness in eliciting immune responses in mice.

Simplified

Herpes zoster (HZ), caused by varicella zoster virus (VZV) reactivation commonly in elderly/immuno-compromised individuals, leads to tremendous social burden. Despite approved vaccines, there is an urgent need for longer-lasting and more effective HZ vaccines. This study designs a novel mRNA-LNP vaccine targeting VZV glycoprotein E (gE), with the assistance of AI technology, achieving effective and enduring prevention against VZV infection with favorable safety. From numerous empirically designed antigen sequences, AI-based screening identifies promising candidate variants, which are systematically evaluated based on their humoral and cellular immune responses in BALB/c mice. The study further explores the underlying correlation between the cellular localization and immunogenicity of the vaccine candidates and screens 5'UTR elements affecting mRNA expression. A 4-week administration interval and immunogenicity are subsequently validated via detection of gE-specific IgG antibodies and CD4T-cell responses in mice. Notably, the vaccine VZV-gEmD elicits strong humoral response, including gE-specific IgG antibodies and VZV-specific antibodies in rhesus macaques. The CD4T-cell responses, critical for VZV reactivation protection, are significantly stronger and longer lasting with VZV-gEmD than with Shingrix. These findings highlight its potential as an effective prophylactic vaccine for HZ and provide confidence for the utilization of this mRNA platform in VZV vaccine development. + +

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Competing interests

G.S.S., K.D., Y.F.L, and Y.T.Z. have a granted patent (CN118240844B) that discloses the preparation method and application of an mRNA vaccine for VZV prevention. G.S.S. holds granted patents (CN114044741B in China, US12171876B2 in US, JP7606722B1 in Japan) pertaining to Lipid YK‐009, which delineate the characteristics of the compound, the formulations that incorporate it, and its potential applications. The remaining authors declare no competing interests.

PubMed

Strong and Lasting Immune Response from Lipid Nanoparticle mRNA Vaccine Against Shingles Developed Using AI

Abstract

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Competing interests

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