Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey

Abstract In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund’s adjuvant and the difference in amino acid sequences in epitopes be...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Munehisa Shimamura, Koichi Kaikita, Hironori Nakagami, Tomohiro Kawano, Nan Ju, Hiroki Hayashi, Ryo Nakamaru, Shota Yoshida, Tsutomu Sasaki, Hideki Mochizuki, Kenichi Tsujita, Ryuichi Morishita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75054d98bf174a6881ebb26034462b6a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:75054d98bf174a6881ebb26034462b6a
record_format	dspace
spelling	oai:doaj.org-article:75054d98bf174a6881ebb26034462b6a2021-12-02T15:02:23ZDevelopment of anti-thrombotic vaccine against human S100A9 in rhesus monkey10.1038/s41598-021-91153-y2045-2322https://doaj.org/article/75054d98bf174a6881ebb26034462b6a2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91153-yhttps://doaj.org/toc/2045-2322Abstract In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund’s adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.Munehisa ShimamuraKoichi KaikitaHironori NakagamiTomohiro KawanoNan JuHiroki HayashiRyo NakamaruShota YoshidaTsutomu SasakiHideki MochizukiKenichi TsujitaRyuichi MorishitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Munehisa Shimamura Koichi Kaikita Hironori Nakagami Tomohiro Kawano Nan Ju Hiroki Hayashi Ryo Nakamaru Shota Yoshida Tsutomu Sasaki Hideki Mochizuki Kenichi Tsujita Ryuichi Morishita Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
description	Abstract In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund’s adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.
format	article
author	Munehisa Shimamura Koichi Kaikita Hironori Nakagami Tomohiro Kawano Nan Ju Hiroki Hayashi Ryo Nakamaru Shota Yoshida Tsutomu Sasaki Hideki Mochizuki Kenichi Tsujita Ryuichi Morishita
author_facet	Munehisa Shimamura Koichi Kaikita Hironori Nakagami Tomohiro Kawano Nan Ju Hiroki Hayashi Ryo Nakamaru Shota Yoshida Tsutomu Sasaki Hideki Mochizuki Kenichi Tsujita Ryuichi Morishita
author_sort	Munehisa Shimamura
title	Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
title_short	Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
title_full	Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
title_fullStr	Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
title_full_unstemmed	Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
title_sort	development of anti-thrombotic vaccine against human s100a9 in rhesus monkey
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/75054d98bf174a6881ebb26034462b6a
work_keys_str_mv	AT munehisashimamura developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT koichikaikita developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT hironorinakagami developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT tomohirokawano developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT nanju developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT hirokihayashi developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT ryonakamaru developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT shotayoshida developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT tsutomusasaki developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT hidekimochizuki developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT kenichitsujita developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey AT ryuichimorishita developmentofantithromboticvaccineagainsthumans100a9inrhesusmonkey
_version_	1718389144385748992

Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey

Ejemplares similares