{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:04:03Z","timestamp":1783652643438,"version":"3.55.0"},"reference-count":10,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,2,20]]},"abstract":"<jats:p>\n                    With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV\/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    (\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    ) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, \u201cvial-fillable\u201d powders of bacteria (including\n                    <jats:italic>M. smegmatis<\/jats:italic>\n                    and\n                    <jats:italic>M. bovis<\/jats:italic>\n                    BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4\u00b0C and 25\u00b0C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0611430104","type":"journal-article","created":{"date-parts":[[2007,2,13]],"date-time":"2007-02-13T21:48:54Z","timestamp":1171403334000},"page":"2591-2595","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":86,"title":["Drying a tuberculosis vaccine without freezing"],"prefix":"10.1073","volume":"104","author":[{"given":"Yun-Ling","family":"Wong","sequence":"first","affiliation":[{"name":"*Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Sampson","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem Andreas","family":"Germishuizen","sequence":"additional","affiliation":[{"name":"*Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunali","family":"Goonesekera","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Caponetti","sequence":"additional","affiliation":[{"name":"Eratech S.r.l., 29100 Piacenza, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Sadoff","sequence":"additional","affiliation":[{"name":"Aeras Global TB Vaccine Foundation, 1405 Research Boulevard, Suite 300, Rockville, MD 20850"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Edwards","sequence":"additional","affiliation":[{"name":"*Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,2,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)88986-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01949-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/79631"},{"key":"e_1_3_4_4_2","first-page":"343","volume":"48","author":"Lind A","year":"1967","unstructured":"A Lind Scand J Respir Dis 48, 343\u2013347 (1967).","journal-title":"Scand J Respir Dis"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/am.24.3.311-317.1972"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/jcis.2000.6740"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018929224005"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018910200420"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-6946(02)00040-7"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.1997.0143"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0611430104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:36:56Z","timestamp":1649774216000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0611430104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,2,20]]},"references-count":10,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,2,20]]}},"alternative-id":["10.1073\/pnas.0611430104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0611430104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,2,20]]},"assertion":[{"value":"2006-10-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}