Oral Immunization of Mice with Cell Extracts from Recombinant Lactococcus lactis Expressing SARS-CoV-2 Spike Protein

Xuan, Biao; Park, Jongbin; Yoo, Jeong Ho; Kim, Eun Bae

doi:10.1007/s00284-022-02866-w

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…Mucosal immunity significantly contributes to the defense against viral pathogens by providing a frontline barrier and an effective immune response. Immunization via oral vaccine administration, incorporating specific antigens, stimulates the synthesis of secretory immunoglobulin A (IgA) on mucosal surfaces ( 33 , 34 ). Studies showed that oral immunization of mice with lactic acid bacteria expressing the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) S1 subunit increased the fecal IgA levels 1.4-fold higher in the immunized mice than controls after two boosting doses on day 22 ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans

Buriev,

Shermatov,

Usmanov

et al. 2024

Front. Nutr.

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Plant-based edible vaccines that provide two-layered protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outweigh the currently used parenteral types of vaccines, which predominantly cause a systemic immune response. Here, we engineered and selected a transgenic tomato genotype (TOMAVAC) that stably synthesized an antigenic S1 protein of SARS-CoV-2. Two-course spaced force-feeding of mice with ≈5.4 μg/ml TOMAVAC increased up to 16-fold the synthesis of RBD-specific NAbs in blood serum and the significant induction of S-IgA in intestinal lavage fluid. In a surrogate virus neutralization test, TOMAVAC-induced NAbs had 15–25% viral neutralizing activity. The results suggested early evidence of the immunogenicity and protectivity of TOMAVAC against the coronavirus disease 2019 (COVID-19) infection. Furthermore, we observed a positive trend of statistically significant 1.2-fold (average of +42.28 BAU/ml) weekly increase in NAbs in the volunteers' serum relative to the initial day. No severe side effects were observed, preliminarily supporting the safety of TOMAVAC. With the completion of future large-scale studies, higher-generation TOMAVAC should be a cost-effective, ecologically friendly, and widely applicable novel-generation COVID-19 vaccine, providing two-layered protection against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans

Buriev,

Shermatov,

Usmanov

et al. 2024

Front. Nutr.

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“…In these contexts, gmLAB expressing therapeutic proteins have been evaluated as next-generation probiotics and microbial therapeutics [26][27][28]. For example, the effectiveness of oral administration of an L. lactis strain expressing the SARS-CoV-2 spike protein has been studied for COVID-19 vaccination [29]. Therefore, in the present study, we constructed gmLAB that express CC12.1scFv and assessed its immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Development of a Single-Chain Fragment Variable that Binds to the SARS-CoV-2 Spike Protein Produced by Genetically Modified Lactic Acid Bacteria

et al. 2023

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SARS-CoV-2 enters cells via binding of the surface-exposed spike protein RBD to host cell ACE2 receptors. Therefore, in this study, we designed a scFv (single-chain fragment variable) based on the amino acid sequence of CC12.1, a neutralizing antibody found in the serum of patients with COVID-19. scFv is a low-molecular-weight antibody designed based on the antibody-antigen recognition site. Compared with the original antibody, scFv has the advantages of high tissue penetration and low production cost. In this study, we constructed gmLAB (genetically modified lactic acid bacteria) by incorporating the designed scFv into a gene expression vector and introducing it into lactic acid bacteria, aiming to develop microbial therapeutics against COVID-19. In addition, gmLAB were also constructed to produce GFP-fused scFv as a means of visualizing scFv. Expression of each scFv was confirmed by Western blotting, and the ability to bind to the RBD was investigated by ELISA. This study is the first to design a scFv against the RBD of SARS-CoV-2 using gmLAB and could be applied in the future.

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“…In particular, L. lactis has been engineered as a live vehicle for the delivery of DNA vaccines and production of therapeutic biomolecules ( Tavares et al, 2020 ). In bacterial cell extracts study, cell extracts from recombinant L. lactis expressing SARS-CoV-2 spike protein were used to oral immunize mice, and antigen-specific antibodies were produced from immunized mice ( Xuan et al, 2022 ). L. lactis IL1403 is a representative laboratory strain that can be used to produce recombinant heterologous proteins ( Tavares et al, 2020 ), and there is no evidence to date that metabolites of L. lactis IL1403 are toxic to experimental animals.…”

Section: Discussionmentioning

confidence: 99%

Oral Administration of Mice with Cell Extracts of Recombinant Lactococcus lactis IL1403 Expressing Mouse Receptor Activator of NF-kB Ligand (RANKL)

Xuan¹,

Park²,

Lee³

et al. 2022

Food Sci Anim Resour

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Oral Immunization of Mice with Cell Extracts from Recombinant Lactococcus lactis Expressing SARS-CoV-2 Spike Protein

Cited by 7 publications

References 28 publications

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans

Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans

Development of a Single-Chain Fragment Variable that Binds to the SARS-CoV-2 Spike Protein Produced by Genetically Modified Lactic Acid Bacteria

Oral Administration of Mice with Cell Extracts of Recombinant Lactococcus lactis IL1403 Expressing Mouse Receptor Activator of NF-kB Ligand (RANKL)

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