Sökning: onr:"swepub:oai:DiVA.org:umu-187297" > Modern Development ...
Fältnamn | Indikatorer | Metadata |
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000 | 03957naa a2200457 4500 | |
001 | oai:DiVA.org:umu-187297 | |
003 | SwePub | |
008 | 210909s2021 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1872972 URI |
024 | 7 | a https://doi.org/10.3390/pathogens100707952 DOI |
040 | a (SwePub)umu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Conlan, J. Wayne4 aut |
245 | 1 0 | a Modern Development and Production of a New Live Attenuated Bacterial Vaccine, SCHU S4 Delta clpB, to Prevent Tularemia |
264 | c 2021-06-23 | |
264 | 1 | b MDPI,c 2021 |
338 | a electronic2 rdacarrier | |
520 | a Inhalation of small numbers of Francisella tularensis subspecies tularensis (Ftt) in the form of small particle aerosols causes severe morbidity and mortality in people and many animal species. For this reason, Ftt was developed into a bona fide biological weapon by the USA, by the former USSR, and their respective allies during the previous century. Although such weapons were never deployed, the 9/11 attack quickly followed by the Amerithrax attack led the U.S. government to seek novel countermeasures against a select group of pathogens, including Ftt. Between 2005-2009, we pursued a novel live vaccine against Ftt by deleting putative virulence genes from a fully virulent strain of the pathogen, SCHU S4. These mutants were screened in a mouse model, in which the vaccine candidates were first administered intradermally (ID) to determine their degree of attenuation. Subsequently, mice that survived a high dose ID inoculation were challenged by aerosol or intranasally (IN) with virulent strains of Ftt. We used the current unlicensed live vaccine strain (LVS), first discovered over 70 years ago, as a comparator in the same model. After screening 60 mutants, we found only one, SCHU S4 Delta clpB, that outperformed LVS in the mouse ID vaccination-respiratory-challenge model. Currently, SCHU S4 Delta clpB has been manufactured under current good manufacturing practice conditions, and tested for safety and efficacy in mice, rats, and macaques. The steps necessary for advancing SCHU S4 Delta clpB to this late stage of development are detailed herein. These include developing a body of data supporting the attenuation of SCHU S4 Delta clpB to a degree sufficient for removal from the U.S. Select Agent list and for human use; optimizing SCHU S4 Delta clpB vaccine production, scale up, and long-term storage; and developing appropriate quality control testing approaches. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Mikrobiologi inom det medicinska området0 (SwePub)301092 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Microbiology in the medical area0 (SwePub)301092 hsv//eng |
653 | a tularemia | |
653 | a Francisella tularensis | |
653 | a live attenuated vaccine | |
653 | a product development | |
700 | 1 | a Sjöstedt, Andersu Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för klinisk mikrobiologi4 aut0 (Swepub:umu)ansj0004 |
700 | 1 | a Gelhaus, H. Carl4 aut |
700 | 1 | a Fleming, Perry4 aut |
700 | 1 | a McRae, Kevan4 aut |
700 | 1 | a Cobb, Ronald R.4 aut |
700 | 1 | a De Pascalis, Roberto4 aut |
700 | 1 | a Elkins, Karen L.4 aut |
710 | 2 | a Umeå universitetb Molekylär Infektionsmedicin, Sverige (MIMS)4 org |
773 | 0 | t Pathogensd : MDPIg 10:7q 10:7x 2076-0817 |
856 | 4 | u https://doi.org/10.3390/pathogens10070795y Fulltext |
856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1592463/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u http://umu.diva-portal.org/smash/get/diva2:1592463/FULLTEXT01 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-187297 |
856 | 4 8 | u https://doi.org/10.3390/pathogens10070795 |
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