Virus-like particles against infectious disease and cancer: guidance for the nano-architect

Rory A Hills1, Mark Howarth1

  • 1Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.

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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