Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines

Abstract We have developed two candidate vaccines to protect against multiple strains of Strep A infections. The candidates are combinatorial synthetic peptide vaccines composed of a M protein epitope (J8 or p*17) and a non-M protein epitope (K4S2). To enhance immunogenicity, each peptide is conjuga...

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Autores principales:	Simone Reynolds, Manisha Pandey, Jessica Dooley, Ainslie Calcutt, Michael Batzloff, Victoria Ozberk, Jamie-Lee Mills, Michael Good
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9658d25da71b425b9c969603708be127
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spelling	oai:doaj.org-article:9658d25da71b425b9c969603708be1272021-12-02T15:14:14ZPreclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines10.1038/s41598-020-80508-62045-2322https://doaj.org/article/9658d25da71b425b9c969603708be1272021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80508-6https://doaj.org/toc/2045-2322Abstract We have developed two candidate vaccines to protect against multiple strains of Strep A infections. The candidates are combinatorial synthetic peptide vaccines composed of a M protein epitope (J8 or p17) and a non-M protein epitope (K4S2). To enhance immunogenicity, each peptide is conjugated to the carrier protein CRM197 (CRM) and formulated with aluminium hydroxide adjuvant Alhydrogel (Alum) to make the final vaccines, J8-CRM + K4S2-CRM/Alum and p17-CRM + K4S2-CRM/Alum. The safety and toxicity of each vaccine was assessed. Sprague Dawley rats were administered three intramuscular doses, over a six-week study with a 4-week recovery period. A control group received CRM only formulated with Alum (CRM/Alum). There was no evidence of systemic toxicity in the rats administered either vaccine. There was an associated increase in white blood cell, lymphocyte and monocyte counts, increased adrenal gland weights, adrenocortical hypertrophy, and increased severity of granulomatous inflammation at the sites of injection and the associated inguinal lymph nodes. These changes were considered non-adverse. All rats administered vaccine developed a robust and sustained immunological response. The absence of clinical toxicity and the development of an immunological response in the rats suggests that the vaccines are safe for use in a phase 1 clinical trial in healthy humans.Simone ReynoldsManisha PandeyJessica DooleyAinslie CalcuttMichael BatzloffVictoria OzberkJamie-Lee MillsMichael GoodNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simone Reynolds Manisha Pandey Jessica Dooley Ainslie Calcutt Michael Batzloff Victoria Ozberk Jamie-Lee Mills Michael Good Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
description	Abstract We have developed two candidate vaccines to protect against multiple strains of Strep A infections. The candidates are combinatorial synthetic peptide vaccines composed of a M protein epitope (J8 or p17) and a non-M protein epitope (K4S2). To enhance immunogenicity, each peptide is conjugated to the carrier protein CRM197 (CRM) and formulated with aluminium hydroxide adjuvant Alhydrogel (Alum) to make the final vaccines, J8-CRM + K4S2-CRM/Alum and p17-CRM + K4S2-CRM/Alum. The safety and toxicity of each vaccine was assessed. Sprague Dawley rats were administered three intramuscular doses, over a six-week study with a 4-week recovery period. A control group received CRM only formulated with Alum (CRM/Alum). There was no evidence of systemic toxicity in the rats administered either vaccine. There was an associated increase in white blood cell, lymphocyte and monocyte counts, increased adrenal gland weights, adrenocortical hypertrophy, and increased severity of granulomatous inflammation at the sites of injection and the associated inguinal lymph nodes. These changes were considered non-adverse. All rats administered vaccine developed a robust and sustained immunological response. The absence of clinical toxicity and the development of an immunological response in the rats suggests that the vaccines are safe for use in a phase 1 clinical trial in healthy humans.
format	article
author	Simone Reynolds Manisha Pandey Jessica Dooley Ainslie Calcutt Michael Batzloff Victoria Ozberk Jamie-Lee Mills Michael Good
author_facet	Simone Reynolds Manisha Pandey Jessica Dooley Ainslie Calcutt Michael Batzloff Victoria Ozberk Jamie-Lee Mills Michael Good
author_sort	Simone Reynolds
title	Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
title_short	Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
title_full	Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
title_fullStr	Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
title_full_unstemmed	Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines
title_sort	preclinical safety and immunogenicity of streptococcus pyogenes (strep a) peptide vaccines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9658d25da71b425b9c969603708be127
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Preclinical safety and immunogenicity of Streptococcus pyogenes (Strep A) peptide vaccines

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