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Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform.

Jaeyoung ParkJulie A Champion
Published in: ACS nano (2023)
There remains a need for the development of a universal influenza vaccine, as current seasonal influenza vaccines exhibit limited protection against mismatched, mutated, or pandemic influenza viruses. A desirable approach to developing an effective universal influenza vaccine is the incorporation of highly conserved antigens in a multivalent scaffold that enhances their immunogenicity. Here, we develop a broadly cross-reactive influenza vaccine by functionalizing self-assembled protein nanocages (SAPNs) with multiple copies of the hemagglutinin stalk on the outer surface and matrix protein 2 ectodomain on the inner surface. SAPNs were generated by engineering short coiled coils, and the design was simulated by MD GROMACS. Due to the short sequences, off-target immune responses against empty SAPN scaffolds were not seen in immunized mice. Vaccination with the multivalent SAPNs induces high levels of broadly cross-reactive antibodies of only external antigens, demonstrating tight spatial control over the designed antigen placement. This work demonstrates the use of SAPNs as a potential influenza vaccine.
Keyphrases
  • immune response
  • protein protein
  • dendritic cells
  • sars cov
  • amino acid
  • binding protein
  • blood brain barrier
  • high throughput
  • metabolic syndrome
  • adipose tissue
  • high resolution
  • molecularly imprinted