scholarly journals Unique features of a recombinant haemagglutinin influenza vaccine that influence vaccine performance

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Arun B. Arunachalam ◽  
Penny Post ◽  
Deborah Rudin
Keyword(s):  
Influenza Vaccine ◽  
Adverse Reactions ◽  
Insect Cells ◽  
Age Groups ◽  
Structural Features ◽  
Vector System ◽  
Baculovirus Expression Vector System ◽  
Baculovirus Expression ◽  
Baculovirus Expression Vector ◽  
Protective Antibodies

AbstractThe influenza vaccine field has been constantly evolving to improve the speed, scalability, and flexibility of manufacturing, and to improve the breadth and longevity of the protective immune response across age groups, giving rise to an array of next generation vaccines in development. Among these, the recombinant influenza vaccine tetravalent (RIV4), using a baculovirus expression vector system to express recombinant haemagglutinin (rHA) in insect cells, is the only one to have reached the market and has been studied extensively. We describe how the unique structural features of rHA in RIV4 improve protective immune responses compared to conventional influenza vaccines made from propagated influenza virus. In addition to the sequence integrity, characteristic of recombinant proteins, unique post-translational processing of the rHA in insect cells instills favourable tertiary and quaternary structural features. The absence of protease-driven cleavage and addition of simple N-linked glycans help to preserve and expose certain conserved epitopes on HA molecules, which are likely responsible for the high levels of broadly cross-reactive and protective antibodies with rare specificities observed with RIV4. Furthermore, the presence of uniform compact HA oligomers and absence of egg proteins, viral RNA or process impurities, typically found in conventional vaccines, are expected to eliminate potential adverse reactions to these components in susceptible individuals with the use of RIV4. These distinct structural features and purity of the recombinant HA vaccine thus provide a number of benefits in vaccine performance which can be extended to other viral targets, such as for COVID-19.

The components of shear stress affecting insect cells used with the baculovirus expression vector system

2017 ◽  
Vol 72 (9-10) ◽  
pp. 429-439 ◽  
Author(s):  
Tobias Weidner ◽  
Damir Druzinec ◽  
Martina Mühlmann ◽  
Rainer Buchholz ◽  
Peter Czermak
Keyword(s):  
Surface Area ◽  
Recombinant Proteins ◽  
Expression Vector ◽  
Insect Cells ◽  
Vector System ◽  
Baculovirus Expression Vector System ◽  
Shear Forces ◽  
Baculovirus Expression ◽  
Baculovirus Expression Vector ◽  
Infected Insect

AbstractInsect-based expression platforms such as the baculovirus expression vector system (BEVS) are widely used for the laboratory- and industrial-scale production of recombinant proteins. Thereby, major drawbacks to gain high-quality proteins are the lytic infection cycle and the shear sensitivity of infected insect cells due to turbulence and aeration. Smaller bubbles were formerly assumed to be more harmful than larger ones, but we found that cell damage is also dependent on the concentration of protective agents such as Pluronic®. At the appropriate concentration, Pluronic forms a layer around air bubbles and hinders the attachment of cells, thus limiting the damage. In this context, we used microaeration to vary bubble sizes and confirmed that size is not the most important factor, but the total gas surface area in the reactor is. If the surface area exceeds a certain threshold, the concentration of Pluronic is no longer sufficient for cell protection. To investigate the significance of shear forces, a second study was carried out in which infected insect cells were cultivated in a hollow fiber module to protect them from shear forces. Both model studies revealed important aspects of the design and scale-up of BEVS processes for the production of recombinant proteins.

scholarly journals Induction of Robust and Specific Humoral and Cellular Immune Responses by Bovine Viral Diarrhea Virus Virus-Like Particles (BVDV-VLPs) Engineered with Baculovirus Expression Vector System

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 350
Author(s):  
Zhanhui Wang ◽  
Mengyao Liu ◽  
Haoran Zhao ◽  
Pengpeng Wang ◽  
Wenge Ma ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vector System ◽  
Baculovirus Expression Vector System ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Cellular Immune Responses ◽  
Baculovirus Expression ◽  
Baculovirus Expression Vector ◽  
Cellular Immune ◽  
Viral Diarrhea Virus

Bovine viral diarrhea virus (BVDV) is an important animal pathogen that affects cattle. Infections caused by the virus have resulted in substantial economic losses and outbreaks of BVDV are reported globally. Virus-like particles (VLPs) are promising vaccine technology largely due to their safety and strong ability to elicit robust immune responses. In this study, we developed a strategy to generate BVDV-VLPs using a baculovirus expression vector system (BEVS). We were able to assemble BVDV-VLPs composed of dimerized viral proteins E2 and Erns, and the VLPs were spherical particles with the diameters of about 50 nm. Mice immunized with 15 μg of VLPs adjuvanted with ISA201 elicited higher levels of E2-specific IgG, IgG1, and IgG2a antibodies as well as higher BVDV-neutralizing activity in comparison with controls. Re-stimulation of the splenocytes collected from mice immunized with VLPs led to significantly increased levels of CD3+CD4+T cells and CD3+CD8+T cells. In addition, the splenocytes showed dramatically enhanced proliferation and the secretion of Th1-associated IFN-γ and Th2-associated IL-4 compared to that of the unstimulated control group. Taken together, our data indicate that BVDV-VLPs efficiently induced BVDV-specific humoral and cellular immune responses in mice, showing a promising potential of developing BVDV-VLP-based vaccines for the prevention of BVDV infections.

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