{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:14:36Z","timestamp":1777450476173,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Altern Lab Anim"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016\u20132018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1\u03b2 levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies.<\/jats:p>","DOI":"10.1177\/026119291804600107","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T04:41:33Z","timestamp":1554784893000},"page":"23-37","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Applicability of the Monocyte Activation Test (MAT) in the Quality Control of the 17DD Yellow Fever Vaccine"],"prefix":"10.1177","volume":"46","author":[{"given":"Katherine Antunes","family":"de Mattos","sequence":"first","affiliation":[{"name":"Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiol\u00f3gicos (Bio-Manguinhos), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine Cristina Azevedo","family":"Navega","sequence":"additional","affiliation":[{"name":"Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiol\u00f3gicos (Bio-Manguinhos), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitor Fernandes","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiol\u00f3gicos (Bio-Manguinhos), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra Santos","family":"Almeida","sequence":"additional","affiliation":[{"name":"Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiol\u00f3gicos (Bio-Manguinhos), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane Caldeira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia e Toxicologia, Instituto Nacional de Controle da Qualidade em Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Octavio Augusto Fran\u00e7a","family":"Presgrave","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia e Toxicologia, Instituto Nacional de Controle da Qualidade em Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel da Silva Guedes","family":"Junior","sequence":"additional","affiliation":[{"name":"Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiol\u00f3gicos (Bio-Manguinhos), Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Fernandes","family":"Delgado","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia e Toxicologia, Instituto Nacional de Controle da Qualidade em Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"bibr1-026119291804600107","unstructured":"Anon. (2017). COES Febre Amarela, Informe 43\/2017, 7 pp. Bras\u00edlia-DF, Brazil: Minist\u00e9rio da Sa\u00fade. Available at: http:\/\/portalarquivos.saude.gov.br\/images\/pdf\/2017\/junho\/02\/COES-FEBRE-AMARELA-INFORME-43-Atualiza-o-em-31maio2017.pdf (Accessed 25.01.18)."},{"key":"bibr2-026119291804600107","unstructured":"Anon. (2017). Monitoramento do Per\u00edodo Sazonal da Febre Amarela Brasil \u2014 2017\/2018, Informe no. 02, 11 pp. Bras\u00edlia-DF, Brazil: Minist\u00e9rio da Sa\u00fade. Available at: http:\/\/portalarquivos2.saude.gov.br\/images\/pdf\/2017\/novembro\/21\/af-informe-febre-amarela-2c.pdf (Accessed 25.01.18)."},{"key":"bibr3-026119291804600107","unstructured":"Anon. (2017). Yellow Fever \u2014 Brazil. Geneva, Switzerland: World Health Organization. Available at: http:\/\/www.who.int\/csr\/don\/27-january-2017-yellow-fever-brazil\/en\/ (Accessed 25.01.18)."},{"key":"bibr4-026119291804600107","unstructured":"PereiraR.C. (2017). Supported by Fiocruz, WHO immunizes 13 million Angolans. Rio de Janeiro, Brazil: Fiocruz. Available at: https:\/\/portal.fiocruz.br\/en\/content\/supported-fiocruz-who-immunizes-13-million-angolans (Accessed 25.01.18)."},{"key":"bibr5-026119291804600107","unstructured":"ValverdeR. (2017). Febre Amarela: Bio-Manguinhos produz at\u00e9 9 milh\u00f5es de doses da vacina por m\u00eas. Rio de Janeiro, Brazil: Fiocruz. Available at: https:\/\/portal.fiocruz.br\/pt-br\/content\/febre-amarela-bio-manguinhos-produz-ate-9-milhoes-de-doses-da-vacina-por-mes (Accessed 25.01.18)."},{"key":"bibr6-026119291804600107","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.11-0525"},{"key":"bibr7-026119291804600107","first-page":"1364","volume-title":"Farmacopeia Brasileira","author":"Anon.","year":"2010"},{"key":"bibr8-026119291804600107","volume-title":"The European Pharmacopoeia","author":"Anon.","year":"2017"},{"key":"bibr9-026119291804600107","unstructured":"Anon. (2012). Guidance for Industry. Pyrogen and Endotoxins Testing: Questions and Answers, 10 pp. Silver Spring, MD, USA: US Food and Drug Administration. Available at: https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM310098.pdf (Accessed 25.01.18)."},{"key":"bibr10-026119291804600107","doi-asserted-by":"publisher","DOI":"10.1590\/S0104-59702003000500009"},{"key":"bibr11-026119291804600107","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.11.060"},{"key":"bibr12-026119291804600107","volume-title":"The European Pharmacopoeia","author":"Anon.","year":"2010"},{"key":"bibr13-026119291804600107","doi-asserted-by":"publisher","DOI":"10.14573\/altex.1503241"},{"key":"bibr14-026119291804600107","unstructured":"Anon. (2008). Validation status of\n                      in vitro\n                      pyrogen test methods. In ICCVAM Test Method Evaluation Report, Section 3, 9\u201318 pp. Durham, NC, USA: ICCVAM. 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