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Endogenous capsid-forming protein ARC for self-assembling nanoparticle vaccines
Yu Li1,2, Xiaofan Zhao2, Jiaqi Tang2
1New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.
Journal of Nanobiotechnology
|August 27, 2024
Summary
Researchers developed novel protein nanoparticles using activated-regulated cytoskeleton-associated protein (ARC) for multivalent antigen display. These ARC-based vaccines effectively stimulate immune responses against Mpox and SARS-CoV-2, even without adjuvants.
Area of Science:
- Biotechnology
- Immunology
- Nanotechnology
Background:
- Nanoscale scaffolds are promising for vaccine design, with protein nanoparticles offering efficient antigen delivery.
- Activated-regulated cytoskeleton-associated protein (ARC) is an endogenous capsid-forming protein with potential for nanocarrier applications.
Purpose of the Study:
- To engineer ARC for multivalent antigen display using a plug-and-play strategy.
- To evaluate the immunogenicity and efficacy of ARC-based vaccines against Mpox and SARS-CoV-2.
- To investigate the immunostimulatory properties of ARC nanoparticles.
Main Methods:
- Engineering ARC using the SpyCatcher3/SpyTag3 system for antigen conjugation.
- Utilizing ARC's self-assembly capacity for nanoparticle formation.
- Assessing immune responses and protection in challenge models.
Main Results:
- ARC-based vaccines elicited robust immune responses comparable to ferritin-based vaccines against Mpox and SARS-CoV-2.
- ARC nanoparticles acted as immunostimulants, enhancing dendritic cell activation and germinal center responses.
- Adjuvant-free ARC vaccines provided protective immunity in a lethal challenge model.
Conclusions:
- ARC is a feasible novel protein-based nanocarrier for multivalent display of pathogenic antigens.
- Recombinant mammalian retrovirus-like proteins can be exploited as delivery vehicles for bioactive molecules.
- ARC-based vaccines demonstrate significant potential for infectious disease prevention.
