Preclinical safety and immunogenicity of streptococcus pyogenes (strep A) peptide vaccines.
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Date
2021-01-11
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Affiliation(s)
(Reynolds, Pandey, Dooley, Calcutt, Batzloff, Ozberk, Mills, Good) Institute for Glycomics, Griffith University, Gold Coast, Australia
Year
2021
Citation
Scientific Reports. Vol.11(1), 2021.
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Scientific Reports
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Organisation: (LKSIV, LKSIoV) Li Ka Shing Institute of Virology, University of Alberta Organisation No: 501100017001 Country: Canada
Organisation: (NFMRI) National Foundation for Medical Research and Innovation Organisation No: 100008436 Country: Australia
No: 101656 Organisation: National Heart Foundation of Australia Organisation No: 501100001030 Country: Australia
No: APP1160379 Organisation: (NHMRC) National Health and Medical Research Council Organisation No: 501100000925 Country: Australia
No: CRCATSIH CF 001 Organisation: Lowitja Institute Organisation No: 501100004148 Country: Australia
Organisation: (NFMRI) National Foundation for Medical Research and Innovation Organisation No: 100008436 Country: Australia
No: 101656 Organisation: National Heart Foundation of Australia Organisation No: 501100001030 Country: Australia
No: APP1160379 Organisation: (NHMRC) National Health and Medical Research Council Organisation No: 501100000925 Country: Australia
No: CRCATSIH CF 001 Organisation: Lowitja Institute Organisation No: 501100004148 Country: Australia
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 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 p*17-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. Copyright © 2021, The Author(s).
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Article
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Infectious diseases