Lung Transplant Recipients with Sars-cov2 Infection and Bnt162b2 Vaccination Induce Circulating Exosomes with Spike Protein S2 Capable of Inducing Immune Responses to Sars0-cov2 in Mice
1St. Joseph’s Hospital and Medical Center, Phoenix, AZ, 2Yale School of Medicine, New Haven, CT
Meeting: 2022 American Transplant Congress
Abstract number: 44
Keywords: COVID-19, Infection, Lung transplantation
Topic: Clinical Science » Lung » 64 - Lung: All Topics
Session Information
Session Name: Infectious Considerations for Lung Transplantation
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 4:00pm-4:10pm
Location: Hynes Room 210
*Purpose: Exosomes are small vesicles which are released by cells into body fluids. We have demonstrated the presence of circulating exosomes with viral antigens in lung transplant recipients (LTxRs) diagnosed with respiratory viral infections. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection results Covid-19 disease and SARS-CoV2 infection of LTxRs can be severe with poor clinical outcomes. The goal of this single center study is to determine the development of antibody responses specific to SARS-CoV2 in LTxRs, characterize the immune and molecular markers in the circulating exosomes induced and its role in eliciting immunity.
*Methods: To determine that antibody responses and induction of circulating exosomes we enrolled LTxRs with SARS-CoV2 infection (n=50), following 2 doses of vaccination (n=100). Exosomes were isolated from plasma by exosome precipitation kit followed by 0.2 micron filtration and size determination by NanoSight300. Exosomes were subjected to transmission electron microscopy for spike (CSP) and nucleocapsid (CNP) antigens. Exosomes were also characterized by western blot for immune and molecular markers (NFkB, CIITA, 20S proteasome, beta catenin and VWF). C57BL/6 mice were immunized with circulating exosomes isolated from LTxRs with infection.
*Results: 78% of SARS-CoV2 infected LTxRs developed antibodies to CSP and CNP as opposed to normal infected individuals. In contrast, only 55% vaccinated LTxRs developed antibodies to SARS-CoV2 spike. Exosomes from SARS-CoV2 infected and vaccinated individuals contained CSP S2, CNP and immune and molecular markers. Transmission electron microscopy also revealed the presence of CSP and CNP on exosomes. C57BL/6 mice immunized with exosomes carrying CSP developed antibodies to SARS-CoV2 spike antigens. Severe inflammation and lung lesions were also demonstrated in the lungs of mice immunized with exosomes carrying CSP.
*Conclusions: In conclusion, we demonstrated that SARS-CoV2 infected and vaccinated LTxRs induced circulating exosomes with SARS-CoV2 CSP. In addition, exosomes contained important immune activating molecules suggesting that the exosomes induced by SARS-CoV2 may have a physiological role in inducing immune responses. Immunization of mice with exosomes from SARS-CoV2 infected and vaccinated LTxRs not only induced SARS-CoV2 spike specific antibody but also resulted in inflammation and lung lesions in the immunized animals.
To cite this abstract in AMA style:
Bansal S, Tiffany B, Fleming T, Perincheri S, Smith M, Bremner R, Mohanakumar T. Lung Transplant Recipients with Sars-cov2 Infection and Bnt162b2 Vaccination Induce Circulating Exosomes with Spike Protein S2 Capable of Inducing Immune Responses to Sars0-cov2 in Mice [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/lung-transplant-recipients-with-sars-cov2-infection-and-bnt162b2-vaccination-induce-circulating-exosomes-with-spike-protein-s2-capable-of-inducing-immune-responses-to-sars0-cov2-in-mice/. Accessed May 9, 2025.« Back to 2022 American Transplant Congress