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

Chunhong Dong, Wandi Zhu, Lai Wei, Joo Kyung Kim, Yao Ma, Sang-Moo Kang and Bao-Zhong Wang ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50087-5

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