Announcement
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Novel Therapeutic Limits Chronic Inflammation in Animal Models of Chronic Inflammation. P Iversen1, P Kempaiah2, G Dorn2, E Campbell2, Z Kakabadze3, E Ramacciotti4, J Fareed2. 1.Oregon State University, Corvallis, OR, USA.2Loyola University Medical Center, Maywood, IL, USA.3Tbilisi State Medical University, Tbilisi, Georgia.4Science Valley Research Institute, Sao Paulo, Brazil |
Abstract
Background. Elevated levels of TNFα are associated with an increased risk of thrombotic events in various pathological conditions. A peptide vaccine targeting only pathogenic forms of sTNFR2 while preserving the membrane-bound (wild-type) TNFR2 can lower circulating TNFα leading to less inflammation. Objectives. These studies investigate the therapeutic effect of a 14 amino acid sTNFR2-targeting peptide vaccine. We hypothesize vaccinating animals will mediate clearance of sTNRF2 bound TNFα leading to less inflammation and diminished thrombosis. Methods. 32 adult caspace-1 biosensor mice (16 male and 16 female) were divided into four groups: 1) saline, 2) alum control, 3) low dose vaccine (0.025 mg), and 4) high dose (0.75) vaccine on day 0 and day 14. Endpoints included body weight, organ weights, antibodies to the vaccine and inflammation reported by caspace-1 activity. 24 Adult Lewis rats were divided into three groups: 1) saline control, 2) low dose vaccine (0.025 mg), and 3) high dose vaccine (0.075 mg) 21 days prior to inferior vena cava ligation. Endpoints include measures of thrombus formation, 4 hours post ligation and measures of thrombin. Results. The vaccine was well tolerated in the biosensor mouse with no changes in body weight or organ weights. No pro-inflammatory responses were detected. No acute changes in inflammatory response were observed, indicating the peptide itself is not active. Significant reductions in inflammatory responses were detected for the low dose vaccination. The reductions may represent a novel measure of vaccine efficacy. In the rat inferior vena cava ligation study, a significant reduction in thrombus formation was observed:15 mg in PBS (Grp 1) to 11 mg in low dose (Grp 2) (p<0.00001) and 15 mg in PBS (Grp 1) to 7 mg in high dose (Grp 3) (p<0.00001). Significant reductions in thrombin were also observed: 29 in PBS (Grp 1) to 26 in low dose (Grp 2) (p<0.00001) and 29 in PBS (Grp 1) to 27 in high dose (Grp 3) (p<0.00001). Conclusions. Novel interventions into management of chronic inflammation are needed. The peptide vaccine is well tolerated and effective in reducing chronic inflammation. In addition, the vaccine reduced thrombosis in a rat model. These findings provide a basis to further evaluate this novel vaccine in follow-up pre-clinical studies.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.