Immunization with DNA prime-subunit protein boost strategy based on influenza H9N2 virus conserved matrix protein M1 and its epitope screening

Liu, Fen; Wang, Xueliang; Zheng, Mou‐Xiong; Xiong, Feifei; Liu, Xueying; Zhou, Linting; Tan, Wen‐Song; Chen, Ze

doi:10.1038/s41598-020-60783-z

Cited by 15 publications

(14 citation statements)

References 45 publications

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“…described combined vaccinations with the plasmid DNA pCAG-optiF-2 prime + protein roptiF-2 boost vaccination strategy, eliciting more robust immunity, as confirmed by the detection of antibodies against NDV using enzyme-linked immunosorbent assay and virus neutralization assay, when compared to those vaccinated with only the plasmid pCAG-optiF-2 or protein roptiF-2, providing more efficacious protection against the virulent NDV challenge. Similar results were also observed regarding the H9N2 influenza virus [ 6 ], Campylobacter jejuni [ 7 ], and the H5N1 influenza virus [ 8 ]. However, there is still no report using plasmid DNA together with protein as immunogens in poultry.…”

Section: Introductionsupporting

confidence: 80%

In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus

et al. 2021

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The Cre-recombinase mediated in vivo minicircle DNA vaccine platform (CRIM) provided a novel option to replace a traditional DNA vaccine. To further improve the immune response of our CRIM vaccine, we designed a dual promoter expression plasmid named pYL87 which could synthesize short HN protein under a prokaryotic in vivo promoter PpagC and full length HN protein of genotype VII Newcastle disease virus (NDV) under the previous eukaryotic CMV promoter at the same time. Making use of the self-lysed Salmonella strain as a delivery vesicle, chickens immunized with the pYL87 construction showed an increased serum haemagglutination inhibition antibody response, as well as an increased cell proliferation level and cellular IL-4 and IL-18 cytokines, compared with the previous CRIM vector pYL47. After the virus challenge, the pYL87 vector could provide 80% protection compared to 50% protection against genotype VII NDV in pYL47 immunized chickens, indicating a promising dual promoter strategy used in vaccine design.

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Section: Introductionsupporting

confidence: 80%

In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus

et al. 2021

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“…Recent advances in computational biology, immunoinformatics, and reverse vaccinology can facilitate in designing safe and efficient vaccines in a time and cost-effective manner [29,98]. Biological data such as genomics and proteomics are being used to mine potential epitopes, design long lasting immunogenic subunit vaccine and laboratory validation of that candidate [99,100]. Therefore, the present study was undertaken to screen out the potential immunodominant B cell as well as CTL and HTL epitopes from all different structural and non-structural proteins of WNV virus through immunoinformatics approach to design a safe, chimeric multi-subunit vaccine against the human host.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus

et al. 2021

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West Nile Virus (WNV) is a life threatening flavivirus that causes significant morbidity and mortality worldwide. No preventive therapeutics including vaccines against WNV are available for human use. In this study, immunoinformatics approach was performed to design a multi epitope-based subunit vaccine against this deadly pathogen. Human (HLA) and Mice (H-2) allele specific potential T-cell and B-cell epitopes were shortlisted through a stringent procedure. Molecular docking showed selected epitopes that have stronger binding affinity with human TLR-4. Molecular dynamics simulation confirmed the stable nature of the docked complex. Furthermore, in silico cloning analysis ensures efficient expression of desired gene in the microbial system. Interestingly, previous studies showed that two of our selected epitopes have strong immune response against WNV. Therefore, selected epitopes could be strong vaccine candidates to prevent WNV infections in human. However, further in vitro and in vivo investigations could be strengthening the validation of the vaccine candidate against WNV.

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“…However, some reports have suggested a protective role of CD8 + T cells in controlling Zika virus replication in mice and nonhuman primates ( 21 , 22 ) and dengue virus replication in mice ( 23 , 24 ). When we take T-cell-mediated immune responses by IFN-γ production into account, DNA priming-protein boosting vaccination is superior to protein immunization alone ( 25 – 27 ). While S1 and SΔTM protein immunization induced neutralizing antibodies against both pseudovirions and the wild-type MERS-CoV strain, they did not induce IFN-γ production in response to antigen peptide stimulation.…”

Section: Discussionmentioning

confidence: 99%

Cross-Protection against MERS-CoV by Prime-Boost Vaccination Using Viral Spike DNA and Protein

Choi

Goo

Yang

et al. 2020

J Virol

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Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and has a high mortality of ∼34%. However, since its discovery in 2012, an effective vaccine has not been developed for it. To develop a vaccine against multiple strains of MERS-CoV, we targeted spike glycoprotein (S) using prime-boost vaccination with DNA and insect cell-expressed recombinant proteins for the receptor-binding domain (RBD), S1, S2, SΔTM, or SΔER. Our S subunits were generated using an S sequence derived from the MERS-CoV EMC/2012 strain. We examined humoral and cellular immune responses of various combinations with DNA plasmids and recombinant proteins in mice. Mouse sera immunized with SΔER DNA priming/SΔTM protein boosting showed cross-neutralization against 15 variants of S-pseudovirions and the wild-type KOR/KNIH/002 strain. In addition, these immunizations provided full protection against the KOR/KNIH/002 strain challenge in human DPP4 knock-in mice. These findings suggest that vaccination with the S subunits derived from one viral strain can provide cross-protection against variant MERS-CoV strains with mutations in S. DNA priming/protein boosting increased interferon-γ (IFN-γ) production, while protein-alone immunization did not. The RBD subunit alone was insufficient to induce neutralizing antibodies, suggesting the importance of structural conformation. In conclusion, heterologous DNA priming with protein boosting is an effective way to induce both neutralizing antibodies and cell-mediated immune responses for MERS-CoV vaccine development. This study suggests a strategy for selecting a suitable platform for developing vaccines against MERS-CoV or other emerging coronaviruses. Importance Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild-type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines.

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Immunization with DNA prime-subunit protein boost strategy based on influenza H9N2 virus conserved matrix protein M1 and its epitope screening

Cited by 15 publications

References 45 publications

In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus

In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus

Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus

Cross-Protection against MERS-CoV by Prime-Boost Vaccination Using Viral Spike DNA and Protein

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