Logo Medical Science Monitor Basic Research

Call: 1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research

15 May 2013

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

Wei-Xin DuBCEFG, Bao-Wen ChenBCDFG, Jin-Biao LuBCD, Meng-Qiu GaoBD, Xiao-Bing ShenB, Lei YangB, Cheng SuB, Guo-Zhi WangADG, Qing-feng SunB, Miao XuACDG

DOI: 10.12659/MSMBR.883912

Med Sci Monit Basic Res 2013; 19:1460-152

Abstract

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 AND 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.

Keywords: Immunization, Guinea Pigs, Drug Evaluation, Preclinical, Dose-Response Relationship, Immunologic, Bacterial Proteins - immunology, Antigens, Bacterial - immunology, Recombinant Proteins - immunology, Tuberculin - immunology, Tuberculin Test, young adult

Add Comment 0 Comments

In Press

Clinical Research  

Questionnaire-Based Study of 392 Women in Abbottabad, Pakistan, to Evaluate the Types of Cosmetic Products ...

Med Sci Monit Basic Res In Press; DOI:  

Most Viewed Current Articles

15 Jun 2022 : Clinical Research  

Evaluation of Apical Leakage After Root Canal Obturation with Glass Ionomer, Resin, and Zinc Oxide Eugenol ...

DOI :10.12659/MSMBR.936675

Med Sci Monit Basic Res 2022; 28:e936675

07 Jul 2022 : Laboratory Research  

Cytotoxicity, Apoptosis, Migration Inhibition, and Autophagy-Induced by Crude Ricin from Ricinus communis S...

DOI :10.12659/MSMBR.936683

Med Sci Monit Basic Res 2022; 28:e936683

01 Jun 2022 : Laboratory Research  

Comparison of Sealing Abilities Among Zinc Oxide Eugenol Root-Canal Filling Cement, Antibacterial Biocerami...

DOI :10.12659/MSMBR.936319

Med Sci Monit Basic Res 2022; 28:e936319

17 Jan 2022 : Clinical Research  

Anodal Transcranial Direct Current Stimulation (tDCS) Over the Primary Motor Cortex (M1) Enhances Motor Res...

DOI :10.12659/MSMBR.934180

Med Sci Monit Basic Res 2022; 28:e934180

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416