{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:47:46Z","timestamp":1784260066079,"version":"3.55.0"},"reference-count":7,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background Vaccination against tuberculosis is one of the most successful\n                    medical measures to reduce morbidity and mortality. The BCG vaccine has been in\n                    use for more than 100 years, but its efficacy is still controversial. New\n                    vaccine candidates may offer better protection than available BCG vaccine. In\n                    this work, we studied the acute and the repeated-dose toxicity study of a new\n                    vector vaccine TB\/Flu-04L against tuberculosis.<\/jats:p><jats:p>\n          Materials and Methods The study was conducted on 60 BALB\/c mice\n                    and 150 Wistar rats. The vaccine was administered intranasally and intravenously\n                    for the acute toxicity study. For the repeated-dose toxicity study, rats were\n                    intranasally immunized by 6.5 log10 TCID50 or 7.5\n                        log10 TCID50 three times with 21-day intervals.\n                    Mortality, temperature, body weight, food and water consumption, hematological\n                    and biochemical parameters, urine analysis, as well as cardiovascular,\n                    respiratory, and central nervous system parameters were evaluated. A macroscopic\n                    examination of internal organs was performed.<\/jats:p><jats:p>\n          Results The TB\/FLU-04L vaccine did not cause death among the mice\n                    and rats in the acute toxicity study. There were no pathological abnormalities\n                    in animal condition, behavior, food and water consumption, temperature, and body\n                    weight during the observation period. The results suggest that intranasal\n                    repeated-dose administration of the TB\/FLU-04L vaccine does not exhibit\n                    significant toxicity in rats.<\/jats:p><jats:p>Hematological and biochemistry analysis and the histological examination\n                    identified no toxicity-associated changes.<\/jats:p><jats:p>\n          Conclusions The toxicity study in mice and rats showed that the intranasal\n                    vector vaccine TB\/FLU-04L had no toxic effect. The tests confirm no\n                    adverse effects for laboratory animals in the studied parameters.<\/jats:p>","DOI":"10.1055\/a-1771-5985","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T23:50:54Z","timestamp":1649289054000},"page":"215-219","source":"Crossref","is-referenced-by-count":9,"title":["Preclinical Safety Evaluation: Acute and Repeated-Dose Toxicity of a\n                    New Intranasal Recombinant Vector Vaccine TB\/FLU-04L Against\n                    Tuberculosis"],"prefix":"10.1055","volume":"72","author":[{"given":"Kira","family":"Stosman","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Sivak","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Aleksandrov","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanna","family":"Buzitskaya","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Rassokha","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Stukova","sequence":"additional","affiliation":[{"name":"Department of preclinical trials, Smorodintsev Research Institute of\n                    Influenza, St. Petersburg, Russian Federation (SRII)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"2003300","DOI":"10.1183\/13993003.03300-2020","article-title":"World Health Organization recommendations on the treatment of drug-resistant\n                    tuberculosis, 2020 update","volume":"57","author":"F Mirzayev","year":"2021","journal-title":"Eur Respir J"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S1473-3099(13)70030-6","article-title":"Drug-resistant tuberculosis: time for visionary political leadership. Lancet\n                    Infect","volume":"13","author":"I Abubakar","year":"2013","journal-title":"Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"316","DOI":"10.3389\/fimmu.2020.00316","article-title":"Vaccination against tuberculosis: Revamping BCG by molecular genetics guided by\n                    immunology","volume":"11","author":"SH E Kaufmann","year":"2020","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1038\/nm1213","article-title":"Mucosal immunity and vaccines","volume":"11","author":"J Holmgren","year":"2005","journal-title":"Nat Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.it.2018.01.006.","article-title":"New tuberculosis vaccine strategies: taking aim at un-natural immunity","volume":"39","author":"M Jeyanathan","year":"2018","journal-title":"Trends Immunol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10096-020-03843-6","article-title":"Tuberculosis vaccine development: from classic to clinical candidates","volume":"1","author":"J Li","year":"2020","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"ref8","first-page":"536","volume-title":"A manual for conducting pre-clinical study of medicinal products. Part 2","author":"A N Mironov","year":"2012"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1771-5985.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T23:53:06Z","timestamp":1649289186000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1771-5985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":7,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2022,4,6]]},"published-print":{"date-parts":[[2022,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1771-5985","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"value":"2194-9379","type":"print"},{"value":"2194-9387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4]]}}}