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Enhancing cross-protection against influenza by heterologous sequential immunization with mRNA LNP and protein nanoparticle vaccines

Author

Listed:
  • Chunhong Dong

    (Georgia State University Institute for Biomedical Sciences)

  • Wandi Zhu

    (Georgia State University Institute for Biomedical Sciences)

  • Lai Wei

    (Georgia State University Institute for Biomedical Sciences)

  • Joo Kyung Kim

    (Georgia State University Institute for Biomedical Sciences)

  • Yao Ma

    (Georgia State University Institute for Biomedical Sciences)

  • Sang-Moo Kang

    (Georgia State University Institute for Biomedical Sciences)

  • Bao-Zhong Wang

    (Georgia State University Institute for Biomedical Sciences)

Abstract

Enhancing influenza vaccine cross-protection is imperative to alleviate the significant public health burden of influenza. Heterologous sequential immunization may synergize diverse vaccine formulations and routes to improve vaccine potency and breadth. Here we investigate the effects of immunization strategies on the generation of cross-protective immune responses in female Balb/c mice, utilizing mRNA lipid nanoparticle (LNP) and protein-based PHC nanoparticle vaccines targeting influenza hemagglutinin. Our findings emphasize the crucial role of priming vaccination in shaping Th bias and immunodominance hierarchies. mRNA LNP prime favors Th1-leaning responses, while PHC prime elicits Th2-skewing responses. We demonstrate that cellular and mucosal immune responses are pivotal correlates of cross-protection against influenza. Notably, intranasal PHC immunization outperforms its intramuscular counterpart in inducing mucosal immunity and conferring cross-protection. Sequential mRNA LNP prime and intranasal PHC boost demonstrate optimal cross-protection against antigenically drifted and shifted influenza strains. Our study offers valuable insights into tailoring immunization strategies to optimize influenza vaccine effectiveness.

Suggested Citation

  • Chunhong Dong & Wandi Zhu & Lai Wei & Joo Kyung Kim & Yao Ma & Sang-Moo Kang & Bao-Zhong Wang, 2024. "Enhancing cross-protection against influenza by heterologous sequential immunization with mRNA LNP and protein nanoparticle vaccines," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50087-5
    DOI: 10.1038/s41467-024-50087-5
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    References listed on IDEAS

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    1. Lawrence R. Shiow & David B. Rosen & Naděžda Brdičková & Ying Xu & Jinping An & Lewis L. Lanier & Jason G. Cyster & Mehrdad Matloubian, 2006. "CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs," Nature, Nature, vol. 440(7083), pages 540-544, March.
    2. Dennis Lapuente & Jana Fuchs & Jonas Willar & Ana Vieira Antão & Valentina Eberlein & Nadja Uhlig & Leila Issmail & Anna Schmidt & Friederike Oltmanns & Antonia Sophia Peter & Sandra Mueller-Schmucker, 2021. "Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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