Trimeric, APC-Targeted Subunit Vaccines Protect Mice against Seasonal and Pandemic Influenza

Tjärnhage, Elias; Brown, Diamond; Bogen, Bjarne; Andersen, Tor Kristian; Grødeland, Gunnveig

doi:10.1128/jvi.01694-22

Cited by 4 publications

(3 citation statements)

References 53 publications

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“… 42 Even though, MERS-CoV monomeric RBD or spike protein were able to generate desirable protecting immune responses, other studies with other viruses have shown that trimeric native like oligomeric envelope proteins may induce long lasting immune responses. 43 , 44 Recently, Chang Chi-Chieh et.al have expressed the MERS-CoV-S1 ectodomain trimeric protein in the recombinant baculovirus expression system and showed in the presence of QS-21 adjuvant, that the S1 trimeric proteins were able to elicit a strong and enduring memory T cell response. 45 …”

Section: Discussionmentioning

confidence: 99%

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Ahuja,

Vishwakarma,

Raj

et al. 2024

Human Vaccines & Immunotherapeutics

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVax TM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVax TM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.

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Section: Discussionmentioning

confidence: 99%

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Ahuja,

Vishwakarma,

Raj

et al. 2024

Human Vaccines & Immunotherapeutics

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“…There is still room for improvement and advancement. Differences in cell lines and culture circumstances, particularly in the transition from serum-containing medium to serum-free medium, may have a major impact on the cell properties [23,24].…”

Section: Discussionmentioning

confidence: 99%

The Screening and Mechanism of Influenza-Virus Sensitive MDCK Cell Lines for Influenza Vaccine Production

Yang,

Yu,

et al. 2024

Diseases

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Influenza is a potentially fatal acute respiratory viral disease caused by the influenza virus. Influenza viruses vary in antigenicity and spread rapidly, resulting in seasonal epidemics. Vaccination is the most effective strategy for lowering the incidence and fatality rates of influenza-related disorders, and it is also an important method for reducing seasonal influenza infections. Mammalian Madin–Darby canine kidney (MDCK) cell lines are recommended for influenza virus growth, and such cell lines have been utilized in several commercial influenza vaccine productions. The limit dilution approach was used to screen ATCC-MDCK cell line subcellular strains that are especially sensitive to H1N1, H3N2, BV, and BY influenza viruses to increase virus production, and research on influenza virus culture media was performed to support influenza virus vaccine development. We also used RNA sequencing to identify differentially expressed genes and a GSEA analysis to determine the biological mechanisms underlying the various levels of susceptibility of cells to influenza viruses. MDCK cell subline 2B6 can be cultured to increase titer and the production of the H1N1, H3N2, BV, and BY influenza viruses. MDCK-2B6 has a significantly enriched and activated in ECM receptor interaction, JAK-STAT signaling, and cytokine receptor interaction signaling pathways, which may result in increased cellular susceptibility and cell proliferation activity to influenza viruses, promote viral adsorption and replication, and elevate viral production, ultimately. The study revealed that MDCK-2B6 can increase the influenza virus titer and yield in vaccine production by increasing cell sensitivity and enhancing proliferative activity.

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“…Antigen-presenting cells (APCs), especially DCs, play a critical role in the interaction between innate immunity and adaptive immunity after infection or immunization. Targeting antigens toward molecules or chemokine receptors on APCs, such as CD11c [ 23 ], DEC-205 [ 24 ], Xcr1 [ 25 ], major histocompatibility complex class II (MHC-II) [ 26 ] and macrophage galactose-type lectin (MGL) [ 27 ], could dramatically stimulate enhanced immunogenicity. To date, monoclonal antibodies [ 28 ], single chain variable fragments (scFvs) [ 23 ], nanobodies [ 29 ] and DC-targeting peptides (DCpep) [ 30 ] have been employed in the design of DC-targeting vaccines.…”

Section: Introductionmentioning

confidence: 99%

A novel “prime and pull” strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge

Wang,

He,

Wang

et al. 2023

J Nanobiotechnol

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Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel “prime and pull” strategy for addressing the production of protective TRM cells in vaccine design.

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Trimeric, APC-Targeted Subunit Vaccines Protect Mice against Seasonal and Pandemic Influenza

Cited by 4 publications

References 53 publications

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

The Screening and Mechanism of Influenza-Virus Sensitive MDCK Cell Lines for Influenza Vaccine Production

A novel “prime and pull” strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge

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