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<p>Influenza virus nucleoprotein (NP) is a promising target for universal influenza vaccines due to its conservation and high immunogenicity. Here, we uncovered a previously unknown factor that <i>E. coli</i>-produced NP carries bacterial RNA, which is crucial for its high immunogenicity but may pose safety and consistency concerns due to batch variability. To address these concerns, we developed a NP mutant (NP<sub>mut</sub>) that lacks RNA binding activity but can be loaded with CpG1826, a synthetic oligodeoxynucleotide adjuvant that has been used in the FDA-approved Hepatitis B vaccine. The CpG1826-loaded NP<sub>mut</sub> induced immune responses comparable to RNA-bound NP while eliminating safety risks. Additionally, the mixture of CpG1826-loaded NP<sub>mut</sub> and 3M2e protein (three tandem copies of the ectodomain of influenza M2 protein) provided enhanced protection against influenza viruses challenge. Our findings highlight the adjuvant activity of bacterial RNA in <i>E. coli</i>-produced NP and propose a safer strategy for developing universal influenza vaccines.</p>

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Addressing unexpected bacterial RNA safety concerns of E. coli produced influenza NP through CpG loaded mutant

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月15日

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  • Cen Chen,
  • Mengling Li,
  • Aili Guo,
  • Pengju Guo,
  • Wanpo Zhang,
  • Changqin Gu,
  • Guoyuan Wen,
  • Hongbo Zhou,
  • Pan Tao

摘要

Influenza virus nucleoprotein (NP) is a promising target for universal influenza vaccines due to its conservation and high immunogenicity. Here, we uncovered a previously unknown factor that E. coli-produced NP carries bacterial RNA, which is crucial for its high immunogenicity but may pose safety and consistency concerns due to batch variability. To address these concerns, we developed a NP mutant (NPmut) that lacks RNA binding activity but can be loaded with CpG1826, a synthetic oligodeoxynucleotide adjuvant that has been used in the FDA-approved Hepatitis B vaccine. The CpG1826-loaded NPmut induced immune responses comparable to RNA-bound NP while eliminating safety risks. Additionally, the mixture of CpG1826-loaded NPmut and 3M2e protein (three tandem copies of the ectodomain of influenza M2 protein) provided enhanced protection against influenza viruses challenge. Our findings highlight the adjuvant activity of bacterial RNA in E. coli-produced NP and propose a safer strategy for developing universal influenza vaccines.