Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines

ABSTRACT

Introduction

Vaccination can be effective defense against many infectious agents and the corresponding diseases. Discoveries elucidating the mechanisms of the immune system have given hopes to developing vaccines against diseases recalcitrant to current treatment/prevention strategies. One such finding is the ability of immunogenic biological nanoparticles to powerfully boost the immunogenicity of poorer antigens conjugated to them with virus-like particle (VLP)-based vaccines as a key example. VLPs take advantage of the well-defined molecular structures associated with sub-unit vaccines and the immunostimulatory nature of conjugate vaccines.

Areas Covered

In this review, we will discuss how advances in understanding the immune system can inform VLP-based vaccine design and how VLP-based vaccines have uncovered underlying mechanisms in the immune system.

Expert Opinion

As our understanding of mechanisms underlying the immune system increases, that knowledge should inform our vaccine design. Testing of proof-of-concept vaccines in the lab should seek to elucidate the underlying mechanisms of immune responses. The integration of these approaches will allow for VLP-based vaccines to live up to their promise as a powerful plug-and-play platform for next-generation vaccine development.

KEYWORDS:

• Biomacromolecules
• conjugate vaccines
• mechanism of immune response
• nanoparticles
• virus-like particles

Article highlights

• Virus-like particles (VLPs) are protein-based nanoparticles derived from viruses and recombinantly expressed in various systems (insect, mammalian, plant, and bacterial cells)

• VLPs are powerful carrier proteins capable of potently boosting immune responses against antigens loaded onto/into the VLP.

• Advances in understanding the immune system have helped explain why VLPs are capable of generating potent immune responses. At the same time advances in VLP-based vaccines have further elucidated the mechanisms underlying immune responses. This allows for the rationale design of next generation VLP-based conjugate vaccines.

• VLPs contain huge potential as a next generation plug-and-play vaccine platform allowing for rapid responses to novel diseases. Anti-SARS-CoV-2 VLP-based conjugate vaccines have made it to clinical trials suggesting these vaccine platforms are starting to gain traction.

Acknowledgments

We would like to thank Dr. Herbert Kavunja for the helpful discussions and advice on writing this review.

Declaration of interest

X Huang is the founder of Iaso Therapeutics Inc., which is dedicated to the development of next generation of vaccines using the bacteriophage Qβ platform. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

H. M^cFall-Boegeman and X. Huang designed the project. H. M^cFall-Boegeman researched the topic and prepared the original manuscript. H. M^cFall-Boegeman and X Huang reviewed and edited the manuscript.

Additional information

Funding

This manuscript was funded by the National Institutes of Health (R01CA225105 and R01AI146210), and Michigan State University.