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Vaccines
Special Issues
Virus-Like Particle Vaccine Development
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Virus-Like Particle Vaccine Development

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Design, Development, and Delivery".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 10061

Special Issue Editor

Dr. Jian Xu

E-Mail Website
Guest Editor
Biology and Information Science Laboratory, East China Normal University, Shanghai 200050, China
Interests: protein production; virology; vaccine; virus-like particle; liposome; experimental evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viruses are now recognized as important resources for studying diseases and producing recombinant proteins. Virus-like particles (VLPs), which imitate viruses but do not possess genetic material, are a safe and powerful tool for vaccine development. There has already been some licensed VLP vaccines available in the commercial market against various infectious pathogens. While VLP subunit vaccines have succeeded, there are still challenges to overcome before the VLP surface display system can be widely employed as an effective vaccine strategy for many infectious diseases.

This Special Issue highlights how the leading researchers design, produce, and approve their VLP vaccines using diverse protein expression systems. We also share various perspectives and discuss the future of the VLP-based vaccine strategy.

Dr. Jian Xu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccine
  • virus-like particle
  • display
  • protein production
  • immunogenicity

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Published Papers (5 papers)

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Research

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15 pages, 1171 KiB  
Article
Virus-like Particles Produced in the Baculovirus System Protect Hares from European Brown Hare Syndrome Virus (EBHSV) Infection
by Giulio Severi, Lucia Anzalone, Laura Madeo, Anna Serroni, Claudia Colabella, Antonella Di Paolo, Pier Mario Mangili, Elisabetta Manuali, Andrea Felici, Monica Cagiola, Antonio Lavazza, Lorenzo Capucci, Giovanni Pezzotti and Antonio De Giuseppe
Vaccines 2025, 13(7), 731; https://doi.org/10.3390/vaccines13070731 - 5 Jul 2025
Viewed by 263
Abstract
Background/Objectives: European Brown Hare Syndrome (EBHS) is an acute and highly contagious viral disease of hares that causes considerable economic losses on wild and captive-reared hares. No preventive treatments are currently available to defeat the disease. Immunoprophylactic and biosafety measures could be applied [...] Read more.
Background/Objectives: European Brown Hare Syndrome (EBHS) is an acute and highly contagious viral disease of hares that causes considerable economic losses on wild and captive-reared hares. No preventive treatments are currently available to defeat the disease. Immunoprophylactic and biosafety measures could be applied to prevent EBHS only in captive-reared hares, where vaccination is proposed as an effective strategy. Due to the lack of a cellular substrate for virus growth, commercially available vaccines are autovaccines produced from inactivated liver suspensions of hares dead for EBHS. Therefore, using a recombinant vaccine based on VP60 major capsid protein seems a viable alternative to overcome such a problem. Methods: the 6xHis C-terminal tagged VP60 protein of EBHSV was expressed and produced in baculovirus, purified by affinity chromatography and the self-assembled recombinant (rEVP60-His6) protein. To establish the protective properties of rEVP60-His6-based VLPs, hares were immunised with 50 and 100 µg of VLPs and parenterally challenged with EBHSV. Results: all hares vaccinated with 100 µg of VLPs survived after the experimental infection, demonstrating the excellent protective ability of this prototype VLPs-based vaccine. Conclusions: self-assembled EBHSV rEVP60-His6 protein was successfully produced following a rapid, simple, low-cost protocol. Although the protective efficacy of such VLPs were experimentally demonstrated, some key aspects remain to be clarified, including the duration of protection, the entity of the antibody response, and the ability to stimulate cell-mediated response. Last, an additional aspect to be evaluated is whether the use of an adjuvant can determine whether its presence improves the performance of the recombinant VLPs vaccine. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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25 pages, 3965 KiB  
Article
Preclinical Development of a Novel Zika Virus-like Particle Vaccine in Combination with Tetravalent Dengue Virus-like Particle Vaccines
by Dominik A. Rothen, Sudip Kumar Dutta, Pascal S. Krenger, Alessandro Pardini, Anne-Cathrine S. Vogt, Romano Josi, Ilva Lieknina, Albert D. M. E. Osterhaus, Mona O. Mohsen, Monique Vogel, Byron Martina, Kaspars Tars and Martin F. Bachmann
Vaccines 2024, 12(9), 1053; https://doi.org/10.3390/vaccines12091053 - 14 Sep 2024
Cited by 1 | Viewed by 2749
Abstract
Declared as a Public Health Emergency in 2016 by the World Health Organization (WHO), the Zika virus (ZIKV) continues to cause outbreaks that are linked to increased neurological complications. Transmitted mainly by Aedes mosquitoes, the virus is spread mostly amongst several tropical regions [...] Read more.
Declared as a Public Health Emergency in 2016 by the World Health Organization (WHO), the Zika virus (ZIKV) continues to cause outbreaks that are linked to increased neurological complications. Transmitted mainly by Aedes mosquitoes, the virus is spread mostly amongst several tropical regions with the potential of territorial expansion due to environmental and ecological changes. The ZIKV envelope protein’s domain III, crucial for vaccine development due to its role in receptor binding and neutralizing antibody targeting, was integrated into sterically optimized AP205 VLPs to create an EDIII-based VLP vaccine. To increase the potential size of domains that can be accommodated by AP205, two AP205 monomers were fused into a dimer, resulting in 90 rather than 180 N-/C- termini amenable for fusion. EDIII displayed on AP205 VLPs has several immunological advantages, like a repetitive surface, a size of 20–200 nm (another PASP), and packaged bacterial RNA as adjuvants (a natural toll-like receptor 7/8 ligand). In this study, we evaluated a novel vaccine candidate for safety and immunogenicity in mice, demonstrating its ability to induce high-affinity, ZIKV-neutralizing antibodies without significant disease-enhancing properties. Due to the close genetical and structural characteristics, the same mosquito vectors, and the same ecological niche of the dengue virus and Zika virus, a vaccine covering all four Dengue viruses (DENV) serotypes as well as ZIKV would be of significant interest. We co-formulated the ZIKV vaccine with recently developed DENV vaccines based on the same AP205 VLP platform and tested the vaccine mix in a murine model. This combinatory vaccine effectively induced a strong humoral immune response and neutralized all five targeted viruses after two doses, with no significant antibody-dependent enhancement (ADE) observed. Overall, these findings highlight the potential of the AP205 VLP-based combinatory vaccine as a promising approach for providing broad protection against DENV and ZIKV infections. Further investigations and preclinical studies are required to advance this vaccine candidate toward potential use in human populations. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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24 pages, 6314 KiB  
Article
Preclinical Evaluation of Novel Sterically Optimized VLP-Based Vaccines against All Four DENV Serotypes
by Dominik A. Rothen, Sudip Kumar Dutta, Pascal S. Krenger, Anne-Cathrine S. Vogt, Ilva Lieknina, Jan M. Sobczak, Albert D. M. E. Osterhaus, Mona O. Mohsen, Monique Vogel, Byron Martina, Kaspars Tars and Martin F. Bachmann
Vaccines 2024, 12(8), 874; https://doi.org/10.3390/vaccines12080874 - 1 Aug 2024
Cited by 6 | Viewed by 2682 | Correction
Abstract
Over the past few decades, dengue fever has emerged as a significant global health threat, affecting tropical and moderate climate regions. Current vaccines have practical limitations, there is a strong need for safer, more effective options. This study introduces novel vaccine candidates covering [...] Read more.
Over the past few decades, dengue fever has emerged as a significant global health threat, affecting tropical and moderate climate regions. Current vaccines have practical limitations, there is a strong need for safer, more effective options. This study introduces novel vaccine candidates covering all four dengue virus (DENV) serotypes using virus-like particles (VLPs), a proven vaccine platform. The dengue virus envelope protein domain III (EDIII), the primary target of DENV-neutralizing antibodies, was either genetically fused or chemically coupled to bacteriophage-derived AP205-VLPs. To facilitate the incorporation of the large EDIII domain, AP205 monomers were dimerized, resulting in sterically optimized VLPs with 90 N- and C-termini. These vaccines induced high-affinity/avidity antibody titers in mice, and confirmed their protective potential by neutralizing different DENV serotypes in vitro. Administration of a tetravalent vaccine induced high neutralizing titers against all four serotypes without producing enhancing antibodies, at least not against DENV2. In conclusion, the vaccine candidates, especially when administered in a combined fashion, exhibit intriguing properties for potential use in the field, and exploring the possibility of conducting a preclinical challenge model to verify protection would be a logical next step. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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18 pages, 11542 KiB  
Article
Gold Nanoparticle Virus-like Particles Presenting SARS-CoV-2 Spike Protein: Synthesis, Biophysical Properties and Immunogenicity in BALB/c Mice
by Vivian A. Salazar, Joan Comenge, Rosa Suárez-López, Judith A. Burger, Rogier W. Sanders, Neus G. Bastús, Carlos Jaime, Joan Joseph-Munne and Victor Puntes
Vaccines 2024, 12(8), 829; https://doi.org/10.3390/vaccines12080829 - 23 Jul 2024
Cited by 4 | Viewed by 2676
Abstract
Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold [...] Read more.
Gold nanoparticles (AuNPs) decorated with antigens have recently emerged as promising tools for vaccine development due to their innate ability to provide stability to antigens and modulate immune responses. In this study, we have engineered deactivated virus-like particles (VLPs) by precisely functionalizing gold cores with coronas comprising the full SARS-CoV-2 spike protein (S). Using BALB/c mice as a model, we investigated the immunogenicity of these S-AuNPs-VLPs. Our results demonstrate that S-AuNPs-VLPs consistently enhanced antigen-specific antibody responses compared to the S protein free in solution. This enhancement included higher binding antibody titers, higher neutralizing capacity of antibodies, and stronger T-cell responses. Compared to the mRNA COVID-19 vaccine, where the S protein is synthesized in situ, S-AuNPs-VLPs induced comparable binding and neutralizing antibody responses, but substantially superior T-cell responses. In conclusion, our study highlights the potential of conjugated AuNPs as an effective antigen-delivery system for protein-based vaccines targeting a broad spectrum of infectious diseases and other emergent viruses. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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Review

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31 pages, 1849 KiB  
Review
The Application of Single-Cell Technologies for Vaccine Development Against Viral Infections
by Hong Nhi Nguyen, Isabel O. Vanderzee and Fei Wen
Vaccines 2025, 13(7), 687; https://doi.org/10.3390/vaccines13070687 - 26 Jun 2025
Viewed by 630
Abstract
The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit [...] Read more.
The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit proteins and virus-like particles (VLPs), and more recently, mRNA-based vaccines, while also enhancing methods for evaluating vaccine performance. Despite these innovations, a persistent challenge remains: the inherent complexity and heterogeneity of immune responses continue to impede efforts to achieve consistently effective and durable protection across diverse populations. Single-cell technologies have emerged as transformative tools for dissecting this immune heterogeneity, providing comprehensive and granular insights into cellular phenotypes, functional states, and dynamic host–pathogen interactions. In this review, we examine how single-cell epigenomic, transcriptomic, proteomic, and multi-omics approaches are being integrated across all stages of vaccine development—from infection-informed discovery to guide vaccine design, to high-resolution evaluation of efficacy, and refinement of cell lines for manufacturing. Through representative studies, we highlight how insights from these technologies contribute to the rational design of more effective vaccines and support the development of personalized vaccination strategies. Full article
(This article belongs to the Special Issue Virus-Like Particle Vaccine Development)
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