A new study offers valuable insights into tailoring immunization strategies to optimize influenza vaccine effectiveness.

To offer cross-protection against diverse influenza virus variants, nanoparticle vaccines can produce pivotal cellular and mucosal immune responses that enhance vaccine efficacy and broaden protection, according to the study in Nature Communications .

To alleviate the significant public health burden of influenza epidemics and occasional pandemics, it’s essential to enhance influenza vaccine cross-protection, researchers say.

While the Centers for Disease Control and Prevention (CDC) recommends annual influenza vaccination, current seasonal influenza vaccines typically provide strain-specific and short-lived immunity. Seasonal influenza vaccines offer limited cross-protection against antigenically diverse virus variants and provide no defense against sporadic influenza pandemics, the authors explain.

“Developing effective influenza vaccines or vaccination strategies that can confer cross-protection against variant influenza viruses is a high priority to mitigate the public health consequences of influenza,” says first author Chunhong Dong, a postdoctoral fellow in the Institute for Biomedical Sciences at Georgia State.

In the study, the researchers investigated the effects of immunization strategies on the generation of cross-protective immune responses in female mice using mRNA lipid nanoparticle (LNP) and protein-based polyethyleneimine-HA/CpG (PHC) nanoparticle vaccines targeting influenza hemagglutinin . The mice were immunized with either intramuscular mRNA LNP or intranasal PHC vaccines in a typical prime-plus-boost regimen. A variety of sequential immunization strategies were included in this study for comparison.

“We demonstrated that cellular and mucosal immune responses are pivotal correlates of cross-protection against influenza,” says Baozhong Wang, senior author of the study and a professor in the Institute for Biomedical Sciences.

“Notably, intranasal PHC immunization outperforms its intramuscular counterpart in inducing mucosal immunity and conferring cross-protection. Sequential mRNA LNP prime and intranasal PHC boost demonstrated optimal cross-protection against antigenically drifted and shifted influenza strains.”

The study highlights the importance of immunization orders and indicates that in a sequential immunization, an mRNA vaccine priming plays an important role in steering the Th1/Th2 immune responses. Also, the intranasal PHC boost is crucial to the induction of mucosal immunity, Wang says.

The National Institutes of Health/National Institute of Allergy and Infectious Diseases funded the work.

Source: Georgia State

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