Inhalation with ACE-2-Expressing-Lung-Exosomes for Prophylactic Protection and Treating SARS-CoV-2 Infection and Disease
Inhalation with ACE-2-Expressing-Lung-Exosomes for Prophylactic Protection and Treating SARS-CoV-2 Infection and Disease
Attapon Cheepsattayakorn1,2,3,4*, Ruangrong Cheepsattayakorn5, Porntep Siriwanarangsun2
1. Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand.
2. Faculty of Medicine, Western University, Pathumtani Province, Thailand.
3. 10th Zonal Tuberculosis and Chest Disease Center, Chiang Mai, Thailand.
4. Department of Disease Control, Ministry of Public Health, Thailand.
5. Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Correspondence to: Attapon Cheepsattayakorn, 10th Zonal Tuberculosis and Chest Disease Center, 143 Sridornchai Road Changklan Muang Chiang Mai 50100 Thailand.
Copyright
© 2024 Attapon Cheepsattayakorn. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 28 March 2024
Published: 01 May 2024
Inhalation with ACE-2-Expressing-Lung-Exosomes for Prophylactic Protection and Treating SARS-CoV-2 Infection and Disease
SARS-CoV-2 infectivity depends on binding its S protein with the entry-receptor “ hACE-2 ” a promising strategic treatment, therefore, is this interaction inhibition [1-3]. Some SARS-CoV-2 variants, such as B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants were highly resistant to mRNA-1273 vaccine-induced humoral immunity or BNT162b2 [4-6]. A recent study demonstrated that in a female mouse model, inhalation of ACE-2-expressing-human-lung-spheroid-cells (LSC)-derived exosomes (LSC-Exo) (Figure 1) could protect the host throughout the whole lung by biodistribution and deposition against COVID-19 (SARS-CoV-2) infection by SARS-CoV-2 binding, blocking the interaction of host cells with SARS-CoV-2, and virus neutralization both in vitro and in vivo [7]. This study also revealed decrease of viral loads and protection of SARS-CoV-2-induced disease [7]. Three different types of inhalation devices are commonly used; jet, ultrasonic, and vibrating mesh (all are nebulizer) (Figure 2) [8]. In non-human primates and rats studies, when nebulized with eFlow, human immunoglobulin preparations were deposited into the airways as well as treated-lung alveoli [9]. VR942, an anti-interleukin (IL)-13 mAb is a first-in-class for dry-powder inhalers (DPIs) [10].
In conclusion, ACE-2-expressing-human-lung-spheroid-cells-derived exosomes could be a promising-broad-spectrum bioprotectant against SARS-CoV-2 variants and other emerging virus variants. By using common nebulizer inhalation, it can be administrated other therapeutic agents for treating the patients’ lung and respiratory system.
Figure 1 : A. Demonstrating extraction scheme of LSC and LSC-Exo from healthy donors, created with Biorender.com. B. Demonstrating immunofluorescence staining and quantification analysis of ACE-2 on LSC and HEK. Scale bar: 50 μm. n = 3. C. Demonstrating Western blot quantification of ACE-2 expression in LSC and HEK, which derived from the same experiments and processed in parallel. n = 3. D. Demonstrating representative TEM images of LSC-Exo and HEK-Exo from 3 independent experiments. Scale bar: 100 μm. E. Demonstrating measurements of size distribution of LSC-Exo and HEK-Exo via nanoparticle tracking analysis. Inset: 3-colar dSTORM image of CD63-Alexa Fluor®-488, PE-CD9, APC-CD81 of LSC-Exo or HEK-Exo. F. Demonstrating quantification of ACE-2 expression on LSC-Exo and HEK-Exo by flow cytometry. n = 3 [7].
Figure 2 : Demonstrating potential therapeutic approaches for respiratory delivery of passive immunotherapeutics against SARS-CoV-2 (COVID-19) [8].
References
1. Lan J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE-2 receptor. Nature 2020; 581 : 215-220.
2. Huang X, et al. Nanotechnology-based strategies against SARS-CoV-2 variants. Nat Nanotechnol 2022; 17 : 1027-1037.
3. Zhang L, et al. An ACE-2 decoy can be administered by inhalation and potently targets omicron variants of SARS-CoV-2. EMBO Mol Med 2022; 14 : e16109.
4. Garcia-Beltran WF, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell 2021; 184 : 2372-2383.e2379.
5. Pouwels KB, et al. Effect f Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nat Med 2021; 27 : 2127-2135.
6. Hui KPY, et al. SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo. Nature 2022; 603 : 715-720.
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