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Virus-like particles against infectious disease and cancer: guidance for the nano-architect
1Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Abstract:
Virus-like particles (VLPs) can play important roles in prevention and therapy for infectious diseases and cancer. Here we describe recent advances in rational construction of VLP assemblies, as well as new approaches to enhance long-lasting antibody and CD8+ T cell responses. DNA origami and computational protein design identified optimal spacing of antigens. Chemical biology advances enabled simple and irreversible VLP decoration with protein or polysaccharide antigens. Mosaic VLPs co-displayed antigens to generate cross-reactive antibodies against different influenza strains and coronaviruses. The mode of action of adjuvants inside VLPs was established through knock-outs and repackaging of innate immune stimuli. VLPs themselves showed their power as adjuvants in cancer models. Finally, landmark clinical results were obtained against malaria and the SARS-CoV-2 pandemic.
Insights
Recent advances in virus-like particle (VLP) technology enhance vaccine development for infectious diseases and cancer. Novel VLP designs improve immune responses, showing promise in clinical trials for malaria and COVID-19.
Area of Science:
- Vaccinology and immunology
- Biotechnology and protein engineering
- Nanomedicine
Background:
- Virus-like particles (VLPs) are promising platforms for vaccines against infectious diseases and cancer.
- Enhancing long-lasting immune responses, including antibody and CD8+ T cell immunity, is crucial for effective VLP-based vaccines.
- Optimizing antigen presentation and incorporating immune stimulants are key challenges in VLP vaccine design.
Purpose of the Study:
- To review recent advancements in the rational design and construction of VLP assemblies.
- To explore novel strategies for improving the immunogenicity and durability of VLP-based vaccines.
- To highlight the therapeutic and prophylactic potential of VLPs in infectious diseases and cancer, supported by clinical data.
Main Methods:
- Utilizing DNA origami and computational protein design to determine optimal antigen spacing on VLPs.
- Employing chemical biology techniques for efficient and stable VLP decoration with various antigens.
- Developing mosaic VLPs for co-displaying multiple antigens to elicit cross-reactive immune responses.
- Investigating the adjuvant mechanisms of innate immune stimuli within VLPs through genetic manipulation.
Main Results:
- Optimal antigen spacing was identified using DNA origami and computational design.
- Simple and irreversible VLP decoration with protein and polysaccharide antigens was achieved.
- Mosaic VLPs successfully generated cross-reactive antibodies against different influenza strains and coronaviruses.
- The adjuvant function of innate immune stimuli within VLPs was elucidated.
- VLPs demonstrated significant adjuvant effects in cancer models.
- Clinical trials reported landmark results for malaria and SARS-CoV-2 vaccines.
Conclusions:
- Recent innovations in VLP construction and antigen display significantly enhance vaccine efficacy.
- VLPs serve as potent platforms for inducing robust and long-lasting immune responses.
- The clinical success against malaria and SARS-CoV-2 underscores the broad applicability of VLP technology in public health.
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