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Review

Suspended cell lines for inactivated virus vaccine production

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Pages 468-480 | Received 01 Oct 2022, Accepted 11 May 2023, Published online: 23 May 2023

Figures & data

Table 1. Existing cell lines acclimated to suspension for use in vaccine production.

Figure 1. Molecular model of potential target gene interactions in genetically engineered suspension cells. The cell membrane surface contains a large number of adhesion factors, which regulate the activity of adherent cultured cells and promote cell growth and proliferation by mediating the contact between cells and ECM or between cells to activate different signaling pathways. Integrin is an important adhesion factor and activates focal adhesion kinase (FAK) by mediating the contact between cells and ECM. FAK inhibits endogenous apoptosis by activating the PI3K/AKT and ERK pathways, thereby regulating cell growth. Therefore, genes that affect α6β4 integrin expression, namely, Itgb1, Talin-1, Kindlin-2, and HDs, and genes that affect adhesive spots, namely Src-1 and Paxillin, can be used as targets for genetic engineering modifications. The PINCH-1 gene regulates and maintains cell adhesion stability through ILK, parvin, and actin regulatory proteins related to the LIM2-LIM5 domain. Talin-1/kindlin-2/Src-1 and Paxillin/ILK/parvin/PINCH-1 form the adhesive plaque complex. Bridgemen mediates cell-cell adhesion. Plakoglobin is in an important class of signaling and adhesion molecules; it binds to classical cadherin and desmosomal cadherin and regulates the stability and strength of its connection. E-cadherin and α-Catenin, and β-Catenin and P120 form cadherin catenin adhesion complex and affect cell adhesion. E-cadherin plays an adhesive role through the Wnt pathway. The introduction of α-Catenin restores the cell response to JNK inhibition and leads to cell-cell adhesion; therefore, knocking out α-Catenin prevents cells from forming adhesive connections. The red font in the figure indicates the 11 key genes that act between cells or between cells and ECM, which can significantly affect cell adhesion through knockout or overexpression. Siat7e plays a negative regulatory role, while the other genes are positive regulators.

Figure 1. Molecular model of potential target gene interactions in genetically engineered suspension cells. The cell membrane surface contains a large number of adhesion factors, which regulate the activity of adherent cultured cells and promote cell growth and proliferation by mediating the contact between cells and ECM or between cells to activate different signaling pathways. Integrin is an important adhesion factor and activates focal adhesion kinase (FAK) by mediating the contact between cells and ECM. FAK inhibits endogenous apoptosis by activating the PI3K/AKT and ERK pathways, thereby regulating cell growth. Therefore, genes that affect α6β4 integrin expression, namely, Itgb1, Talin-1, Kindlin-2, and HDs, and genes that affect adhesive spots, namely Src-1 and Paxillin, can be used as targets for genetic engineering modifications. The PINCH-1 gene regulates and maintains cell adhesion stability through ILK, parvin, and actin regulatory proteins related to the LIM2-LIM5 domain. Talin-1/kindlin-2/Src-1 and Paxillin/ILK/parvin/PINCH-1 form the adhesive plaque complex. Bridgemen mediates cell-cell adhesion. Plakoglobin is in an important class of signaling and adhesion molecules; it binds to classical cadherin and desmosomal cadherin and regulates the stability and strength of its connection. E-cadherin and α-Catenin, and β-Catenin and P120 form cadherin catenin adhesion complex and affect cell adhesion. E-cadherin plays an adhesive role through the Wnt pathway. The introduction of α-Catenin restores the cell response to JNK inhibition and leads to cell-cell adhesion; therefore, knocking out α-Catenin prevents cells from forming adhesive connections. The red font in the figure indicates the 11 key genes that act between cells or between cells and ECM, which can significantly affect cell adhesion through knockout or overexpression. Siat7e plays a negative regulatory role, while the other genes are positive regulators.

Table 2. Potential genetically engineered cell lines for vaccine production.

Figure 2. Illustration of cell suspension culture methodology.

Figure 2. Illustration of cell suspension culture methodology.

Table 3. The advantages and disadvantages of the suspension acclimation methods.