Virus-like particle vaccines: immunology and formulation for clinical translation

Abstract

Introduction: Virus-like particle (VLP) vaccines face significant challenges in their translation from laboratory models, to routine clinical administration. While some VLP vaccines thrive and are readily adopted into the vaccination schedule, others are restrained by regulatory obstacles, proprietary limitations, or finding their niche amongst the crowded vaccine market. Often the necessity to supplant an existing vaccination regimen possesses an immediate obstacle for the development of a VLP vaccine, despite any preclinical advantages identified over the competition. Novelty, adaptability and formulation compatibility may prove invaluable in helping place VLP vaccines at the forefront of vaccination technology.

Areas covered: The purpose of this review is to outline the diversity of VLP vaccines, VLP-specific immune responses, and to explore how modern formulation and delivery techniques can enhance the clinical relevance and overall success of VLP vaccines.

Expert commentary: The role of formation science, with an emphasis on the diversity of immune responses induced by VLP, is underrepresented amongst clinical trials for VLP vaccines. Harnessing such diversity, particularly through the use of combinations of select excipients and adjuvants, will be paramount in the development of VLP vaccines.

Keywords: Clinical translation; VLP; formulation; immunology; vaccine; virus-like particle.

Figure 1.

Structural biodiversity of VLP. VLP can be produced with a variety of structural morphologies defined by the structure of their parent virus. These morphologies include: (a) mono-layered VLP, usually consisting of a single virus capsid protein; (b) multi-layered VLP, formed from multiple concurrently expressed capsid proteins; (c) enveloped VLP, with a lipid bilayer formed over the VLP capsid; and (d) virosomes, consisting of proteins embedded within a lipid bilayer envelope.

Figure 2.

Intracellular processing of VLP. VLP can be internalized and processed through a variety of intracellular pathways. (a) VLP internalized through non-specific pathways such as phagocytosis and macropinocytosis can be processed, with peptides presented on MHC-II as exogenous antigen. (b) Some VLP can also utilize cross-presentation pathways, facilitating the presentation of peptides on MHC-I [70]. (c) Influenza VLP, in this example an influenza virosome, is internalized through receptor-mediated endocytosis prior to fusion of its envelope with the endosomal membrane [90,92,93]. (d) JCV VLP is thought to utilize the processing pathway of its parent virus to facilitate delivery of exogenous nucleic acids, including clathrin-dependent endocytosis, nuclear trafficking, and uncoating of the capsid within the nucleus [99,100].

Figure 3.

The Roles of Formulation Science in VLP Vaccines. The role of formulation science in VLP vaccine manufacture includes the chemical composition of buffers, preservatives, additives and other stabilizing compounds for maintaining intact VLP. This includes protecting VLP from chemical or physical instability, and enzymatic degradation. Formulations can also include targeted delivery compounds, such as muco-adhesives, and immunogenic components such as adjuvants. Storage and distribution of VLP vaccines, and the subsequent route of administration are also important considerations in formulation science, critical in determining the efficacy and immunogenicity of the vaccine.