Advancements in Vaccine Development: Exploiting Virus-Like Particles for Antigen Presentation


In the era of infectious disease outbreaks and the recent COVID-19 pandemic, the development of effective and efficient vaccines has become an urgent global priority. Traditional vaccine strategies, such as attenuated or inactivated viruses, face limitations in terms of time-consuming manufacturing procedures and cost-effectiveness. As a result, researchers have been exploring alternative approaches to vaccine development, including the use of virus-like particles (VLPs). VLPs are virus-derived artificial nanostructures that mimic native viruses, stimulating the immune system through highly repetitive surface structures. They have been extensively studied as new prophylactic and therapeutic vaccine platforms. They offer improved safety profiles and can deliver various antigens and drugs to different targets within tissues and cells, stimulating both humoral and cellular immune responses. Currently, four VLP-based vaccines against human papilloma virus, malaria, and hepatitis B and E viruses are authorized, with many others in clinical trials. VLPs can be modified to display antigens using various gene engineering technologies, enabling optimal epitope presentation without affecting viral morphology.

In a recent study published in Frontiers in Microbiology, Anete Ogrina, Dr. Ina Balke, Ieva Kalnciema, Dr. Dace Skrastina, Dr. Juris Jansons, Prof. Martin F. Bachmann, and Dr. Andris Zeltins from the Latvian Biomedical Research and Study Centre explored the construction of Escherichia coli expression systems for the generation of eggplant mosaic virus (EMV) VLP-derived vaccines. The researchers employed various principles of antigen incorporation, including direct fusion of EMV coat protein (CP) with a major cat allergen (Feld1), co-expression of antigen-containing and unmodified EMV CPs, and two co-expression variants of EMV VLPs and antigen using synthetic zipper pair 18/17 (SYNZIP 18/17) and coiled-coil-forming peptides E and K (Ecoil/Kcoil). They also chemically coupled recombinant Fel d 1 to EMV VLPs as a control experiment. These approaches provide new antigen presentation platforms, reducing the influence of antigens on VLP spatial structure and self-assembly.

The research team demonstrated that all EMV variants containing major cat allergen Feld1 were successfully produced in E. coli, forming Tymovirus-like VLPs. The immunological evaluation of these vaccine candidates in healthy mice individuals showed high titers of Feld1-specific antibody production. However, a high immune response against the carrier EMV was also observed. Antibody avidity tests revealed specific antibody production for four out of the five vaccine candidates, with more than 50% specificity. The results suggest that the EMV-SZ18/17-Feld1 complex and chemically coupled EMV-Feld1 vaccines show potential for further development.

EMV, a member of the Tymovirus genus, was used as a scaffold for VLP construction. EMV CP VLPs demonstrated suitable morphology and the ability to accommodate comparably long antigen sequences at C-terminal end of EMV CP. This finding open up new possibilities for vaccine development using EMV CP VLPs.

The study compared the EMV VLP platforms with filamentous PVY VLPs previously developed by the same research group. Both platforms elicited high titers of Feld1-specific antibodies, but the EMV-Feld1 vaccines stimulated a stronger Th1 immune response and IgG2a subclass production. The EMV-Feld1 vaccine variants also demonstrated higher antibody avidity and specificity for native Feld 1. Further analysis and evaluation are needed to determine the most suitable candidate for vaccination purposes.

The authors’ study holds significant importance in the field of vaccine development. The following are the key significance of the study: The authors developed a universal vaccine platform allowing the incorporation of different antigens into EMV VLPs. A universal vaccine platform would streamline vaccine manufacturing and distribution, offering a cost-effective and time-efficient solution to combat various infectious diseases. The findings of the study contribute to the ongoing efforts in developing universal vaccine strategies. Moreover, the authors compared the icosahedral EMV-Feld1 VLPs with filamentous potato virus Y-Feld1 VLPs previously developed by the same research group. This comparative analysis provides valuable insights into different VLP-based vaccine platforms and their immunogenicity. It allows researchers to evaluate and refine vaccine designs to optimize immune responses and antibody specificity. Furthermore, the researchers focused on the incorporation of the major cat allergen Feld 1 as a model antigen into EMV VLPs. This opens up possibilities for the development of allergen-specific vaccines targeting common allergens, such as those causing allergic respiratory diseases. By demonstrating the successful production of Feld 1-specific antibodies, the study highlights the potential of VLP-based vaccines in addressing allergies and related health concerns.

The new study also emphasized the use of E. coli expression systems for vaccine production. E. coli-based expression systems offer rapid expression and cost-effective manufacturing of recombinant proteins. By demonstrating successful VLP formation and antigen incorporation in E. coli, the study contributes to the development of scalable and economically viable vaccine manufacturing processes.

In conclusion, Dr. Andris Zeltins and colleagues presented promising advancements in vaccine development using EMV VLPs. The different strategies employed for antigen incorporation highlight the versatility of VLPs as vaccine platforms. The study’s findings contribute to the understanding of antigen presentation and the design of more effective and efficient vaccine candidates. Further research in this area holds the potential to revolutionize vaccine manufacturing and improve global health outcomes.

Advancements in Vaccine Development: Exploiting Virus-Like Particles for Antigen Presentation - Medicine Innovates


Ogrina A, Balke I, Kalnciema I, Skrastina D, Jansons J, Bachmann MF, Zeltins A. Bacterial expression systems based on Tymovirus-like particles for the presentation of vaccine antigens. Front Microbiol. 2023;14:1154990. doi: 10.3389/fmicb.2023.1154990.

Go To Front Microbiol.