Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19

Motallebnezhad, Morteza; Omraninava, Melodi; Ghaleh, Hadi Esmaeili Gouvarchin; Jonaidi-Jafari, Nematollah; Hazrati, A.; Malekpour, Kosar; Bagheri, Yasser; Izadi, Morteza; Ahmadi, Majid

doi:10.1016/j.prp.2022.154280

Cited by 8 publications

(5 citation statements)

References 107 publications

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“…In the vaccine field, the interest in EV-mediated antigen delivery is growing based on the observation that mammalian cells infected with viral pathogens release EVs containing viral constituents able to trigger an immune response [ 37 ]. Moreover, EVs carrying S protein have been detected in infected patients, and their potential role in inducing a humoral specific immune response has been suggested [ 38 , 39 ]. Interestingly, compared to soluble antigens, EV-associated antigens were shown to elicit a stronger cytotoxic CD8+ T response [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pomatto

Gai

Negro³

et al. 2023

Pharmaceutics

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Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (Citrus sinensis) juice (oEVs) were investigated as carriers for oral and intranasal SARS-CoV-2 mRNA vaccine. oEVs were efficiently loaded with different mRNA molecules (coding N, subunit 1 and full S proteins) and the mRNA was protected from degrading stress (including RNase and simulated gastric fluid), delivered to target cells and translated into protein. APC cells stimulated with oEVs loaded with mRNAs induced T lymphocyte activation in vitro. The immunization of mice with oEVs loaded with S1 mRNA via different routes of administration including intramuscular, oral and intranasal stimulated a humoral immune response with production of specific IgM and IgG blocking antibodies and a T cell immune response, as suggested by IFN-γ production by spleen lymphocytes stimulated with S peptide. Oral and intranasal administration also triggered the production of specific IgA, the mucosal barrier in the adaptive immune response. In conclusion, plant-derived EVs represent a useful platform for mRNA-based vaccines administered not only parentally but also orally and intranasally.

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Section: Discussionmentioning

confidence: 99%

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pomatto

Gai

Negro³

et al. 2023

Pharmaceutics

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show abstract

“…In COVID-19 patients, the SARS-CoV-2 Spike (S) protein presented on EVs was correlated with the severity of the disease [ 97 ]. Moreover, S protein-associated EVs detectable in infected patients were suggested to be instrumental in triggering a humoral-specific immune response [ 97 , 98 , 99 ]. Therefore, the possible use of EVs as carriers for viral antigens has been investigated to develop vaccines, as summarized in Table 1 .…”

Section: Evs As a Delivery System For Vaccinesmentioning

confidence: 99%

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Gai,

Pomatto,

Deregibus

et al. 2024

Vaccines

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Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic degradation. This observation has prompted researchers to investigate whether EVs from different sources, including plants, could be used for vaccine delivery. Several studies using human or bacterial EVs expressing mRNA or recombinant SARS-CoV-2 proteins showed induction of a humoral and cell mediated immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have demonstrated advantages in conferring long-lasting immunization and lower toxicity than synthetic nanoparticles. Edible plant-derived EVs were shown to be an alternative to human EVs for vaccine delivery, especially via oral administration. EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation, were stable at room temperature for one year, and were able to trigger a SARS-CoV-2 immune response in mice. Lyophilized oEVs containing the S1 mRNA administered to rats via gavage induced a specific humoral immune response with generation of blocking antibodies, including IgA and Th1 lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and ability to stimulate a humoral and cellular immune response.

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“…In COVID-19 patients, the SARS-CoV-2 Spike (S) protein presented on EVs was correlated with the severity of the disease [97]. Moreover, S protein-associated EVs detectable in infected patients were suggested to be instrumental in triggering a humoralspecific immune response [97][98][99]. Therefore, the possible use of EVs as carriers for viral antigens has been investigated to develop vaccines, as summarized in Table 1.…”

Section: Evs As a Delivery System For Vaccinesmentioning

confidence: 99%

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Gai,

Pomatto,

Deregibus

et al. 2024

Preprint

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Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

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Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19

Cited by 8 publications

References 107 publications

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

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