Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development

Background: Virus-like particles (VLPs) are non-genetic multimeric nanoparticles synthesized through in vitro or in vivo self-assembly of one or more viral structural proteins. Immunogenicity and safety of VLPs make them ideal candidates for vaccine development and efficient nanocarriers for foreign antigens or adjuvants to activate the immune system. Aims: The present study aimed to design and synthesize a chimeric VLP vaccine of the phage Qbeta (Qβ) coat protein presenting the universal epitope of the coronavirus. Methods: The RNA phage Qβ coat protein was designed and synthesized, denoted as Qbeta. The CoV epitope, a universal epitope of coronavirus, was inserted into the C-terminal of Qbeta using genetic recombination, which was designated as Qbeta-CoV. The N-terminal of Qbeta-CoV was successively inserted into the TEV restriction site using mCherry red fluorescent label and modified affinity-purified histidine label 6xHE, which was denoted as HE-Qbeta-CoV. Isopropyl β-D-1-thiogalactopyranoside (IPTG) assessment revealed the expression of Qbeta, Qbeta-CoV, and HE-Qbeta-CoV in the BL21 (DE3) cells. The fusion protein was purified by salting out using ammonium sulfate and affinity chromatography. The morphology of particles was observed using electron microscopy. The female BALB/C mice were immunized intraperitoneally with the Qbeta-CoV and HE-Qbeta-CoV chimeric VLPs vaccines. Their sera were collected for the detection of antibody level and antibody titer using ELISA. The serum is used for the neutralization test of the three viruses of MHV, PEDV, and PDCoV. Results: The results revealed that the fusion proteins Qbeta, Qbeta-CoV, and HE-Qbeta-CoV could all obtain successful expression. Particles with high purity were obtained after purification; the chimeric particles of Qbeta-CoV and HE-Qbeta-CoV were found to be similar to Qbeta particles in morphology and formed chimeric VLPs. In addition, two chimeric VLP vaccines induced specific antibody responses in mice, and the antibodies showed certain neutralizing activity. Conclusion: The successful construction of the chimeric VLPs of the phage Qβ coat protein presenting the universal epitope of coronavirus provides a vaccine form with potential clinical applications for the treatment of coronavirus disease.

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Highly immunogenic influenza virus-like particles containing B-cell-activating factor (BAFF) for multi-subtype vaccine development

Antiviral Research ◽

10.1016/j.antiviral.2019.02.004 ◽

2019 ◽

Vol 164 ◽

pp. 12-22 ◽

Cited By ~ 4

Author(s):

Jo-Yu Hong ◽

Ting-Hsuan Chen ◽

Yu-Jou Chen ◽

Chia-Chyi Liu ◽

Jia-Tsrong Jan ◽

...

Keyword(s):

Influenza Virus ◽

B Cell ◽

Vaccine Development ◽

Virus Like Particles ◽

B Cell Activating Factor

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Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery

Vaccines ◽

10.3390/vaccines8030504 ◽

2020 ◽

Vol 8 (3) ◽

pp. 504

Author(s):

Alejandro González-Mora ◽

Jesús Hernández-Pérez ◽

Hafiz M. N. Iqbal ◽

Marco Rito-Palomares ◽

Jorge Benavides

Keyword(s):

Phage Display ◽

Vaccine Development ◽

Vaccine Delivery ◽

Effective Vaccine ◽

Attractive Alternative ◽

Antigen Delivery ◽

Phage Display Technology ◽

Promising Alternative ◽

Phage Dna ◽

The Future

Vaccines are considered one of the most important bioproducts in medicine. Since the development of the smallpox vaccine in 1796, several types of vaccines for many diseases have been created. However, some vaccines have shown limitations as high cost and low immune responses. In that regard, bacteriophages have been proposed as an attractive alternative for the development of more cost-effective vaccines. Phage-displayed vaccines consists in the expression of antigens on the phage surface. This approach takes advantage of inherent properties of these particles such as their adjuvant capacity, economic production and high stability, among others. To date, three types of phage-based vaccines have been developed: phage-displayed, phage DNA and hybrid phage-DNA vaccines. Typically, phage display technology has been used for the identification of new and protective epitopes, mimotopes and antigens. In this context, phage particles represent a versatile, effective and promising alternative for the development of more effective vaccine delivery systems which should be highly exploited in the future. This review describes current advances in the development of bacteriophage-based vaccines, with special attention to vaccine delivery strategies. Moreover, the immunological aspects of phage-based vaccines, as well as the applications of phage display for vaccine development, are explored. Finally, important challenges and the future of phage-bases vaccines are discussed.

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Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2015.12.1299 ◽

2016 ◽

Vol 137 (2) ◽

pp. 351-357 ◽

Cited By ~ 94

Author(s):

Rudolf Valenta ◽

Raffaela Campana ◽

Margit Focke-Tejkl ◽

Verena Niederberger

Keyword(s):

Specific Immunotherapy ◽

Vaccine Development ◽

Mechanisms Of Action ◽

Recombinant Allergens ◽

Allergen Specific Immunotherapy ◽

The Past ◽

The Future

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Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

10.1101/597831 ◽

2019 ◽

Author(s):

Jo-Anne Chan ◽

David Wetzel ◽

Linda Reiling ◽

Kazutoyo Miura ◽

Damien Drew ◽

...

Keyword(s):

Malaria Vaccine ◽

Vaccine Development ◽

Transmission Blocking ◽

Vaccine Candidates ◽

Virus Like Particles ◽

Malaria Vaccines ◽

Membrane Feeding ◽

B Virus ◽

Vaccine Antigens ◽

Novel Virus

ABSTRACTThe development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.

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Peer Review #1 of "Virus like particles as a platform for cancer vaccine development (v0.2)"

10.7287/peerj.4053v0.2/reviews/1 ◽

2017 ◽

Keyword(s):

Peer Review ◽

Cancer Vaccine ◽

Vaccine Development ◽

Virus Like Particles

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Virus-like Particles in Vaccine Development

10.2217/9781780844176 ◽

2014 ◽

Cited By ~ 1

Author(s):

Franco M Buonaguro ◽

Luigi Buonaguro

Keyword(s):

Vaccine Development ◽

Virus Like Particles

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Production of SARS-CoV-2 virus-like particles in insect cells

10.1101/2021.01.30.428979 ◽

2021 ◽

Author(s):

Youjun Mi ◽

Tao Xie ◽

Bingdong Zhu ◽

Jiying Tan ◽

Xuefeng Li ◽

...

Keyword(s):

Escherichia Coli ◽

Human Health ◽

Insect Cells ◽

Vaccine Development ◽

Recombinant Baculovirus ◽

Expression Plasmid ◽

Virus Like Particles ◽

Recombinant Bacmid ◽

Multiple Cloning Sites ◽

S Genes

ABSTRACTCoronavirus disease (COVID-19) causes a serious threat to human health. To production of SARS-COV-2 virus-like particles (VLPs) in insect cells for vaccine development and scientific research. The E, M and S genes were cloned into multiple cloning sites of the new triple expression plasmid with one p10 promoter, two pPH promoters and three multiple cloning sites. The plasmid was transformed into DH10 BacTMEscherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9™ insect cells to generate recombinant baculovirus. After ExpiSf9™ infected with the recombinant baculovirus, the E, M, and S protein co-expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.

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