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Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates

Background: Our previous studies showed the safe preventive and therapeutic effects of immunization using the nanoliposomal antiPCSK9 vaccine called “Liposomal Immunogenic Fused PCSK9-Tetanus plus Alum adjuvant” (L-IFPTA), in mouse models of atherosclerosis. Here we aimed to ascertain the immunogeni...

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Autores principales: Momtazi-Borojeni, Amir Abbas, Jaafari, Mahmoud R., Banach, Maciej, Gorabi, Armita Mahdavi, Sahraei, Hedayat, Sahebkar, Amirhossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309966/
https://www.ncbi.nlm.nih.gov/pubmed/34358164
http://dx.doi.org/10.3390/vaccines9070749
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author Momtazi-Borojeni, Amir Abbas
Jaafari, Mahmoud R.
Banach, Maciej
Gorabi, Armita Mahdavi
Sahraei, Hedayat
Sahebkar, Amirhossein
author_facet Momtazi-Borojeni, Amir Abbas
Jaafari, Mahmoud R.
Banach, Maciej
Gorabi, Armita Mahdavi
Sahraei, Hedayat
Sahebkar, Amirhossein
author_sort Momtazi-Borojeni, Amir Abbas
collection PubMed
description Background: Our previous studies showed the safe preventive and therapeutic effects of immunization using the nanoliposomal antiPCSK9 vaccine called “Liposomal Immunogenic Fused PCSK9-Tetanus plus Alum adjuvant” (L-IFPTA), in mouse models of atherosclerosis. Here we aimed to ascertain the immunogenicity and safety of the L-IFPTA vaccine in a pre-clinical study in healthy non-human primates. Methods: Five male rhesus macaque monkeys were subcutaneously immunized with the L-IFPTA vaccine, four times with bi-weekly intervals. To evaluate immunogenicity, the plasma antiPCSK9 antibody in immunized monkeys was detected and quantified using the ELISA method. The functionality of the induced antiPCSK9 antibodies was determined by the PCSK9/LDLR in vitro binding assay kit. The safety of the vaccine was tested using the evaluation of several major circulating indicators including plasma lipid alterations, inflammatory biomarkers and organ injury biomarkers. Results: The resultant data indicated that the L-IFPTA vaccine significantly and highly induced the generation of functional and safe antiPCSK9 antibodies in immunized monkeys. Plasma levels of specific biomarkers indicating organ performance including creatinine, urea, uric acid, bilirubin, ALP, AS, ALT and TSH were not significantly altered. After immunization in healthy monkeys, non-prespecified endpoints (plasma levels of TC, LDL-C, VLDL-C and TG) were non-significantly reduced by 11.6 ± 36%; 16 ± 28%; 22 ± 53% and 24 ± 51%, respectively, while HDL-C was slightly increased by 2 ± 64%. There were also no significant changes in plasma levels of pro- and anti-inflammatory biomarkers. Conclusion: The L-IFPTA vaccine could efficiently stimulate the host humoral immune response to produce active antibodies that inhibit plasma PCSK9 while not provoking systemic inflammation and not adversely affecting organ performance.
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spelling pubmed-83099662021-07-25 Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates Momtazi-Borojeni, Amir Abbas Jaafari, Mahmoud R. Banach, Maciej Gorabi, Armita Mahdavi Sahraei, Hedayat Sahebkar, Amirhossein Vaccines (Basel) Article Background: Our previous studies showed the safe preventive and therapeutic effects of immunization using the nanoliposomal antiPCSK9 vaccine called “Liposomal Immunogenic Fused PCSK9-Tetanus plus Alum adjuvant” (L-IFPTA), in mouse models of atherosclerosis. Here we aimed to ascertain the immunogenicity and safety of the L-IFPTA vaccine in a pre-clinical study in healthy non-human primates. Methods: Five male rhesus macaque monkeys were subcutaneously immunized with the L-IFPTA vaccine, four times with bi-weekly intervals. To evaluate immunogenicity, the plasma antiPCSK9 antibody in immunized monkeys was detected and quantified using the ELISA method. The functionality of the induced antiPCSK9 antibodies was determined by the PCSK9/LDLR in vitro binding assay kit. The safety of the vaccine was tested using the evaluation of several major circulating indicators including plasma lipid alterations, inflammatory biomarkers and organ injury biomarkers. Results: The resultant data indicated that the L-IFPTA vaccine significantly and highly induced the generation of functional and safe antiPCSK9 antibodies in immunized monkeys. Plasma levels of specific biomarkers indicating organ performance including creatinine, urea, uric acid, bilirubin, ALP, AS, ALT and TSH were not significantly altered. After immunization in healthy monkeys, non-prespecified endpoints (plasma levels of TC, LDL-C, VLDL-C and TG) were non-significantly reduced by 11.6 ± 36%; 16 ± 28%; 22 ± 53% and 24 ± 51%, respectively, while HDL-C was slightly increased by 2 ± 64%. There were also no significant changes in plasma levels of pro- and anti-inflammatory biomarkers. Conclusion: The L-IFPTA vaccine could efficiently stimulate the host humoral immune response to produce active antibodies that inhibit plasma PCSK9 while not provoking systemic inflammation and not adversely affecting organ performance. MDPI 2021-07-06 /pmc/articles/PMC8309966/ /pubmed/34358164 http://dx.doi.org/10.3390/vaccines9070749 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Momtazi-Borojeni, Amir Abbas
Jaafari, Mahmoud R.
Banach, Maciej
Gorabi, Armita Mahdavi
Sahraei, Hedayat
Sahebkar, Amirhossein
Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title_full Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title_fullStr Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title_full_unstemmed Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title_short Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates
title_sort pre-clinical evaluation of the nanoliposomal antipcsk9 vaccine in healthy non-human primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309966/
https://www.ncbi.nlm.nih.gov/pubmed/34358164
http://dx.doi.org/10.3390/vaccines9070749
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