tetano
Editor, Senior Moderator
ACS Nano
. 2023 Dec 12.
doi: 10.1021/acsnano.3c07669. Online ahead of print. Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform
Jaeyoung Park[SUP] 1 [/SUP], Julie A Champion[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Cross-reactive influenza vaccine; Nanoparticle; Self-assembled protein nanocage; Simulation; Subunit vaccine.
. 2023 Dec 12.
doi: 10.1021/acsnano.3c07669. Online ahead of print. Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform
Jaeyoung Park[SUP] 1 [/SUP], Julie A Champion[SUP] 1 [/SUP]
Affiliations
- PMID: 38084728
- DOI: 10.1021/acsnano.3c07669
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.
Keywords: Cross-reactive influenza vaccine; Nanoparticle; Self-assembled protein nanocage; Simulation; Subunit vaccine.