Influenza Virus-like Particle (VLP) Vaccines Expressing the SARS-CoV-2 S Glycoprotein, S1, or S2 Domains

Chu, Ki Back; Kang, Hae Ji; Yoon, Keon Woong; Lee, Hae Ahm; Moon, Eun Kyung; Han, Beom Ku; Quan, Fu‐Shi

doi:10.3390/vaccines9080920

Cited by 20 publications

(19 citation statements)

References 53 publications

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“…Recently, an influenza virus-based SARS-CoV-2 VLP construct was reported, with the vaccine produced in SF9 cells by the co-transfection of baculovirus plasmids expressing S and M1 proteins. In this study, mice receiving the VLPs elicited neutralizing antibodies; however, the vaccine efficacy was not evaluated [ 22 ]. While we have also used influenza virus M1 as the structural basis for VLP self-assembly, our development of an S-M1-expressing cell line that constitutively releases VLPs into the cell culture supernatant will greatly facilitate cost-effective and large-scale VLP production.…”

Section: Discussionmentioning

confidence: 99%

“…In another case, the transient expression of SARS-CoV-S glycoprotein and an influenza matrix (M1) in insect cells was reported, which self-assembled into VLPs capable of inducing neutralizing antibodies and protecting mice from lethal challenges [ 21 ]. More recently, the same approach was used to display SARS-CoV-2 S [ 22 ]. Although the vaccine could induce neutralizing antibodies in mice, its protective efficacy remains to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice

et al. 2022

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Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. In this study, we generated a chimeric VLP-based COVID-19 vaccine stably produced by HEK293T cells. The chimeric VLPs contain the influenza virus A matrix (M1) proteins and the SARS-CoV-2 Wuhan strain spike (S) proteins with a deletion of the polybasic furin cleavage motif and a replacement of the transmembrane and cytoplasmic tail with that of the influenza virus hemagglutinin (HA). These resulting chimeric S-M1 VLPs, displaying S and M1, were observed to be enveloped particles that are heterogeneous in shape and size. The intramuscular vaccination of BALB/c mice in a prime-boost regimen elicited high titers of S-specific IgG and neutralizing antibodies. After immunization and a challenge with SARS-CoV-2 in K18-hACE2 mice, the S-M1 VLP vaccination resulted in a drastic reduction in viremia, as well as a decreased viral load in the lungs and improved survival rates compared to the control mice. Balanced Th1 and Th2 responses of activated S-specific T-cells were observed. Moderate degrees of inflammation and viral RNA in the lungs and brains were observed in the vaccinated group; however, brain lesion scores were less than in the PBS control. Overall, we demonstrate the immunogenicity of a chimeric VLP-based COVID-19 vaccine which confers strong protection against SARS-CoV-2 viremia in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice

et al. 2022

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“…Each component would be self-assembled in insect cells, forming a VLP. As for the second technique, the recombinant baculovirus expressing the full-length S, S1, or S2 proteins was co-transfected with another recombinant baculovirus expressing influenza matrix protein 1 (M1) to form VLP in the insect cells [ 62 ]. In the third technique, the S1 protein was coupled to the bacteriophage AP205 VLP nanoparticles [ 63 ].…”

Section: Application Of Baculovirus Expression Vector System (Bev) Fo...mentioning

confidence: 99%

Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review

Azali

Mohamed

Harun

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background The baculovirus expression vector system has been developed for expressing a wide range of proteins, including enzymes, glycoproteins, recombinant viruses, and vaccines. The availability of the SARS-CoV-2 genome sequence has enabled the synthesis of SARS-CoV2 proteins in a baculovirus-insect cell platform for various applications. Main body of the abstract The most cloned SARS-CoV-2 protein is the spike protein, which plays a critical role in SARS-CoV-2 infection. It is available in its whole length or as subunits like S1 or the receptor-binding domain (RBD). Non-structural proteins (Nsps), another recombinant SARS-CoV-2 protein generated by the baculovirus expression vector system (BEV), are used in the identification of new medications or the repurposing of existing therapies for the treatment of COVID-19. Non-SARS-CoV-2 proteins generated by BEV for SARS-CoV-2 diagnosis or treatment include moloney murine leukemia virus reverse transcriptase (MMLVRT), angiotensin converting enzyme 2 (ACE2), therapeutic proteins, and recombinant antibodies. The recombinant proteins were modified to boost the yield or to stabilize the protein. Conclusion This review covers the wide application of the recombinant protein produced using the baculovirus expression technology for COVID-19 research. A lot of improvements have been made to produce functional proteins with high yields. However, there is still room for improvement and there are parts of this field of research that have not been investigated yet.

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“…VLPs were stored at −80 • C until use. To confirm that the majority of the rBVs were removed from the VLPs, a monolayer of Sf9 cells was infected with the VLPs along with respective controls as described previously [35,36]. Cells were monitored daily for 4 days, and cellular infectivities were assessed under the microscope.…”

Section: Cloning Of Avian Influenza Antigens and Generation Of Rbvs And Vlpsmentioning

confidence: 99%

Neuraminidase in Virus-like Particles Contributes to the Protection against High Dose of Avian Influenza Virus Challenge Infection

et al. 2021

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Neuraminidase is an important target for influenza vaccination. In this study, we generated avian influenza VLPs, expressing hemagglutinin (HA), neuraminidase (NA), HA and NA co-expressed (HANA), to evaluate the protective role of NA against a high (10LD50) and low (2LD50) dose of avian influenza virus challenge infections. A single immunization with HANA VLPs elicited the highest level of virus-specific IgG, IgG1, and IgG2a responses from the sera post-vaccination and the lungs post-challenge-infection. Potent antibody-secreting cell responses were observed from the spleens and lungs of HANA-VLP-immunized mice post-challenge-infection. HANA VLPs induced the highest CD4+ T cell, CD8+ T cell, and germinal center B cells, while strongly limiting inflammatory cytokine production in the lungs compared to other VLP immunization groups. In correlation with these findings, the lowest bodyweight losses and lung virus titers were observed from HANA VLP immunization, and all of the immunized mice survived irrespective of the challenge dose. Contrastingly, VLPs expressing either HA or NA alone failed to elicit complete protection. These results indicated that NA in VLPs played a critical role in inducing protection against a high dose of the challenge infection.

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Influenza Virus-like Particle (VLP) Vaccines Expressing the SARS-CoV-2 S Glycoprotein, S1, or S2 Domains

Cited by 20 publications

References 53 publications

Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice

Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice

Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review

Neuraminidase in Virus-like Particles Contributes to the Protection against High Dose of Avian Influenza Virus Challenge Infection

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