Virus-Like Particles: Revolutionary Platforms for Developing Vaccines Against Emerging Infectious Diseases

Abstract

Virus-like particles (VLPs) are nanostructures that possess diverse applications in therapeutics, immunization, and diagnostics. With the recent advancements in biomedical engineering technologies, commercially available VLP-based vaccines are being extensively used to combat infectious diseases, whereas many more are in different stages of development in clinical studies. Because of their desired characteristics in terms of efficacy, safety, and diversity, VLP-based approaches might become more recurrent in the years to come. However, some production and fabrication challenges must be addressed before VLP-based approaches can be widely used in therapeutics. This review offers insight into the recent VLP-based vaccines development, with an emphasis on their characteristics, expression systems, and potential applicability as ideal candidates to combat emerging virulent pathogens. Finally, the potential of VLP-based vaccine as viable and efficient immunizing agents to induce immunity against virulent infectious agents, including, SARS-CoV-2 and protein nanoparticle-based vaccines has been elaborated. Thus, VLP vaccines may serve as an effective alternative to conventional vaccine strategies in combating emerging infectious diseases.

Keywords: SARS-CoV2; emerging infectious diseases; expression system; vaccine; vaccine development; virus; virus-like particles.

FIGURE 1

A comparison between VLP-based vaccines and the risks associated with conventional vaccines.

FIGURE 2

Production of different types of VLPs and their applications, characteristics, and challenges. (A) Different human pathogenic viruses and parasites, (B) identification of genes that form the structural features of pathogens and can result in the formation of VLPs, (C) incorporation of identified genes in expression vectors such as plasmids, (D) vectors are allowed to express in various expression systems, (E) formation of different VLP types, such as enveloped, non-enveloped, and chimeric VLPs. The non-enveloped VLPs can be of two types: single protein or multiprotein. In multiprotein VLPs, there may be a single layer, multiple layers, and some are mosaic as well. The chimeric VLPs can be modified internally, externally, or can be modified by chemical conjugation.

FIGURE 3

Induction of innate and adaptive immunological responses (A) humoral immunity; (B) cell-mediated immunity) by VLPs, (1) enhanced absorption and presentation of antigens based on VLP by APCs such as dendritic cells, which inform T cells about potential risks, (2) efficient VLP trafficking to lymph nodes, a crucial site for adaptive immunological responses, (3) improved cellular communication between B cells, T cells, and APCs, and (4) the ability of VLP-based antigen to effectively cross-link and activate B cells receptors, which develop into memory cells and long and short lived plasma cells after antigen exposure.

FIGURE 4

Advantages and limitations of different expression systems for the development of virus-like particles.

FIGURE 5

Proposed production system and mechanism of action of SARS-CoV2 virus-like particle vaccine. Plasmids encoding the structural proteins (S, N, M, and E) of the SARS-CoV2 can be transfected into an appropriate mammalian cell line. The assembled VLPs are then collected, purified, and administered to humans. The administration of VLPs stimulates both innate and adaptive immunological responses. If the original SARS-CoV2 enters the human body in the future, memory B cells activate and release antibodies against it. Similarly, the activated CD8+ T cells recognize and kill virus-infected cells.