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Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein

BACKGROUND: To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in preclinical and phase I clinical study. MATERIAL/METHODS: Guinea pigs were sensitized with different Mycobacteria. After sensitization, all animals were intradermally injected...

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Autores principales: Du, Wei-Xin, Chen, Bao-Wen, Lu, Jin-Biao, Gao, Meng-Qiu, Shen, Xiao-Bing, Yang, Lei, Su, Cheng, Wang, Guo-Zhi, Sun, Qing-feng, Xu, Miao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659126/
https://www.ncbi.nlm.nih.gov/pubmed/23676766
http://dx.doi.org/10.12659/MSMBR.883912
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author Du, Wei-Xin
Chen, Bao-Wen
Lu, Jin-Biao
Gao, Meng-Qiu
Shen, Xiao-Bing
Yang, Lei
Su, Cheng
Wang, Guo-Zhi
Sun, Qing-feng
Xu, Miao
author_facet Du, Wei-Xin
Chen, Bao-Wen
Lu, Jin-Biao
Gao, Meng-Qiu
Shen, Xiao-Bing
Yang, Lei
Su, Cheng
Wang, Guo-Zhi
Sun, Qing-feng
Xu, Miao
author_sort Du, Wei-Xin
collection PubMed
description BACKGROUND: To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in preclinical and phase I clinical study. MATERIAL/METHODS: Guinea pigs were sensitized with different Mycobacteria. After sensitization, all animals were intradermally injected with rESAT6 and either PPD or PPD-B. At 24 h after the injection, the erythema of the injection sites were measured using a double-blind method. For the preclinical safety study, different doses of rESAT6 and BSA were given 3 times intramuscularly to guinea pigs. On day 14 after the final immunization, the guinea pigs were intravenously injected with the same reagents in the hind legs and the allergic reactions were observed. A single-center, randomized, open phase I clinical trial was employed. The skin test was conducted in 32 healthy volunteers aged 19–65 years with 0.1 μg, 0.5 μg, and 1 μg rESAT6. Physical examination and laboratory tests were performed before and after the skin test and adverse reactions were monitored. The volunteers’ local and systemic adverse reactions and adverse events were recorded for 7 days. RESULTS: Positive PPD or PPD-B skin tests were observed in all Mycobacteria-sensitized guinea pigs; the diameters of erythema were all >10 mm. The rESAT6 protein induced a positive skin test result in the guinea pigs sensitized with MTB, M. bovis, M. africanum and M. kansasii; the diameters of erythema were 14.7±2.0, 9.3±3.8, 18.7±2.4, and 14.8±4.2 mm, respectively. A negative skin test result was detected in BCG-vaccinated and other NTM-sensitized guinea pigs. The rESAT6 caused no allergic symptoms, but many allergic reactions, such as cough, dyspnea, and even death, were observed in the guinea pigs who were administered BSA. During the phase I clinical trial, no adverse reactions were found in the 0.1 μg rESAT6 group, but in the 0.5 μg rESAT6 group 2 volunteers reported pain and 1 reported itching, and in the 1 μg rESAT6 group there was 1 case of pain, 1 case of itching, and 1 case of blister. No other local or systemic adverse reactions or events were reported. CONCLUSIONS: The rESAT6 can differentiate effectively among MTB infection, BCG vaccination, and NTM infection and is safe in healthy volunteers.
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spelling pubmed-36591262013-05-21 Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein Du, Wei-Xin Chen, Bao-Wen Lu, Jin-Biao Gao, Meng-Qiu Shen, Xiao-Bing Yang, Lei Su, Cheng Wang, Guo-Zhi Sun, Qing-feng Xu, Miao Med Sci Monit Basic Res Animal Studies BACKGROUND: To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in preclinical and phase I clinical study. MATERIAL/METHODS: Guinea pigs were sensitized with different Mycobacteria. After sensitization, all animals were intradermally injected with rESAT6 and either PPD or PPD-B. At 24 h after the injection, the erythema of the injection sites were measured using a double-blind method. For the preclinical safety study, different doses of rESAT6 and BSA were given 3 times intramuscularly to guinea pigs. On day 14 after the final immunization, the guinea pigs were intravenously injected with the same reagents in the hind legs and the allergic reactions were observed. A single-center, randomized, open phase I clinical trial was employed. The skin test was conducted in 32 healthy volunteers aged 19–65 years with 0.1 μg, 0.5 μg, and 1 μg rESAT6. Physical examination and laboratory tests were performed before and after the skin test and adverse reactions were monitored. The volunteers’ local and systemic adverse reactions and adverse events were recorded for 7 days. RESULTS: Positive PPD or PPD-B skin tests were observed in all Mycobacteria-sensitized guinea pigs; the diameters of erythema were all >10 mm. The rESAT6 protein induced a positive skin test result in the guinea pigs sensitized with MTB, M. bovis, M. africanum and M. kansasii; the diameters of erythema were 14.7±2.0, 9.3±3.8, 18.7±2.4, and 14.8±4.2 mm, respectively. A negative skin test result was detected in BCG-vaccinated and other NTM-sensitized guinea pigs. The rESAT6 caused no allergic symptoms, but many allergic reactions, such as cough, dyspnea, and even death, were observed in the guinea pigs who were administered BSA. During the phase I clinical trial, no adverse reactions were found in the 0.1 μg rESAT6 group, but in the 0.5 μg rESAT6 group 2 volunteers reported pain and 1 reported itching, and in the 1 μg rESAT6 group there was 1 case of pain, 1 case of itching, and 1 case of blister. No other local or systemic adverse reactions or events were reported. CONCLUSIONS: The rESAT6 can differentiate effectively among MTB infection, BCG vaccination, and NTM infection and is safe in healthy volunteers. International Scientific Literature, Inc. 2013-05-15 /pmc/articles/PMC3659126/ /pubmed/23676766 http://dx.doi.org/10.12659/MSMBR.883912 Text en © Med Sci Monit, 2013 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
spellingShingle Animal Studies
Du, Wei-Xin
Chen, Bao-Wen
Lu, Jin-Biao
Gao, Meng-Qiu
Shen, Xiao-Bing
Yang, Lei
Su, Cheng
Wang, Guo-Zhi
Sun, Qing-feng
Xu, Miao
Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title_full Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title_fullStr Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title_full_unstemmed Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title_short Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein
title_sort preclinical study and phase i clinical safety evaluation of recombinant mycobacterium tuberculosis esat6 protein
topic Animal Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659126/
https://www.ncbi.nlm.nih.gov/pubmed/23676766
http://dx.doi.org/10.12659/MSMBR.883912
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