Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model
Abstract Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More re...
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| Veröffentlicht in: | The Journal of infectious diseases 2022-04, Vol.225 (8), p.1460-1470 |
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| creator | Fernandez, Jeffrey Sanders, Holly Henn, Jessica Wilson, Jolaine M Malone, Danielle Buoninfante, Alessandra Willms, Matthew Chan, Rita DuMont, Ashley L McLahan, Craig Grubb, Kaitlyn Romanello, Anthony van den Dobbelsteen, Germie Torres, Victor J Poolman, Jan T |
| description | Abstract
Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.
We developed a robust and translational minipig deep surgical wound infection model to better predict the efficacy of Staphylococcus aureus vaccines in human clinical trials. Leucocidin AB was shown to have potential as a vaccine antigen against S. aureus. |
| doi_str_mv | 10.1093/infdis/jiab219 |
| format | Article |
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Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.
We developed a robust and translational minipig deep surgical wound infection model to better predict the efficacy of Staphylococcus aureus vaccines in human clinical trials. Leucocidin AB was shown to have potential as a vaccine antigen against S. aureus.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiab219</identifier><identifier>PMID: 33895843</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Animals ; Bacteria ; Bacterial Load ; Bacterial Proteins ; Clinical trials ; Leukocidin ; Leukocidins ; Major and Brief Reports ; Staphylococcal Infections - microbiology ; Staphylococcal Vaccines ; Staphylococcus aureus ; Surgical site infections ; Surgical Wound Infection - prevention & control ; Swine ; Swine, Miniature ; Toxoids ; Vaccination ; Vaccines ; Wound infection</subject><ispartof>The Journal of infectious diseases, 2022-04, Vol.225 (8), p.1460-1470</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-41f17781a6ee44340fb5d25b92abcb09543d7a24a770a17e8ee33a963dccc6d33</citedby><cites>FETCH-LOGICAL-c452t-41f17781a6ee44340fb5d25b92abcb09543d7a24a770a17e8ee33a963dccc6d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33895843$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernandez, Jeffrey</creatorcontrib><creatorcontrib>Sanders, Holly</creatorcontrib><creatorcontrib>Henn, Jessica</creatorcontrib><creatorcontrib>Wilson, Jolaine M</creatorcontrib><creatorcontrib>Malone, Danielle</creatorcontrib><creatorcontrib>Buoninfante, Alessandra</creatorcontrib><creatorcontrib>Willms, Matthew</creatorcontrib><creatorcontrib>Chan, Rita</creatorcontrib><creatorcontrib>DuMont, Ashley L</creatorcontrib><creatorcontrib>McLahan, Craig</creatorcontrib><creatorcontrib>Grubb, Kaitlyn</creatorcontrib><creatorcontrib>Romanello, Anthony</creatorcontrib><creatorcontrib>van den Dobbelsteen, Germie</creatorcontrib><creatorcontrib>Torres, Victor J</creatorcontrib><creatorcontrib>Poolman, Jan T</creatorcontrib><title>Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.
We developed a robust and translational minipig deep surgical wound infection model to better predict the efficacy of Staphylococcus aureus vaccines in human clinical trials. Leucocidin AB was shown to have potential as a vaccine antigen against S. aureus.</description><subject>Animals</subject><subject>Bacteria</subject><subject>Bacterial Load</subject><subject>Bacterial Proteins</subject><subject>Clinical trials</subject><subject>Leukocidin</subject><subject>Leukocidins</subject><subject>Major and Brief Reports</subject><subject>Staphylococcal Infections - microbiology</subject><subject>Staphylococcal Vaccines</subject><subject>Staphylococcus aureus</subject><subject>Surgical site infections</subject><subject>Surgical Wound Infection - prevention & control</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Toxoids</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Wound infection</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEotvClSOyxAUOaf2VOL4gteWr0lZIFOjRcuzJrpesHey4or-Av41hlwq4cJrDPPPMjN6qekLwMcGSnTg_WJdONk73lMh71YI0TNRtS9j9aoExpTXppDyoDlPaYIw5a8XD6oCxTjYdZ4vq-2dtjPN6dsGjazev0SuYwzc3OLBoCflLMM46j07P0Aew2UBCZ9rMEJ0e0TJoi0pTo6tZT-vbMZhgTE5I5wilXDrvJrcqSpjQVY4rZ8rUdcjeogs_gPm19TJYGB9VDwY9Jni8r0fVpzevP56_q5fv316cny5rwxs615wMRIiO6BaAc8bx0DeWNr2kujc9lg1nVmjKtRBYEwEdAGNatswaY1rL2FH1cuedcr8Fa8DPUY9qim6r460K2qm_O96t1SrcKIlJywUugud7QQxfM6RZbV0yMI7aQ8hJ0YZ0ghPJ2oI--wfdhBx9eU_RtpEYC8q7Qh3vKBNDShGGu2MIVj8zVruM1T7jMvD0zxfu8N-hFuDFDgh5-p_sB-cttTI</recordid><startdate>20220419</startdate><enddate>20220419</enddate><creator>Fernandez, Jeffrey</creator><creator>Sanders, Holly</creator><creator>Henn, Jessica</creator><creator>Wilson, Jolaine M</creator><creator>Malone, Danielle</creator><creator>Buoninfante, Alessandra</creator><creator>Willms, Matthew</creator><creator>Chan, Rita</creator><creator>DuMont, Ashley L</creator><creator>McLahan, Craig</creator><creator>Grubb, Kaitlyn</creator><creator>Romanello, Anthony</creator><creator>van den Dobbelsteen, Germie</creator><creator>Torres, Victor J</creator><creator>Poolman, Jan T</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220419</creationdate><title>Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model</title><author>Fernandez, Jeffrey ; Sanders, Holly ; Henn, Jessica ; Wilson, Jolaine M ; Malone, Danielle ; Buoninfante, Alessandra ; Willms, Matthew ; Chan, Rita ; DuMont, Ashley L ; McLahan, Craig ; Grubb, Kaitlyn ; Romanello, Anthony ; van den Dobbelsteen, Germie ; Torres, Victor J ; Poolman, Jan T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-41f17781a6ee44340fb5d25b92abcb09543d7a24a770a17e8ee33a963dccc6d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Bacteria</topic><topic>Bacterial Load</topic><topic>Bacterial Proteins</topic><topic>Clinical trials</topic><topic>Leukocidin</topic><topic>Leukocidins</topic><topic>Major and Brief Reports</topic><topic>Staphylococcal Infections - microbiology</topic><topic>Staphylococcal Vaccines</topic><topic>Staphylococcus aureus</topic><topic>Surgical site infections</topic><topic>Surgical Wound Infection - prevention & control</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>Toxoids</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Wound infection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernandez, Jeffrey</creatorcontrib><creatorcontrib>Sanders, Holly</creatorcontrib><creatorcontrib>Henn, Jessica</creatorcontrib><creatorcontrib>Wilson, Jolaine M</creatorcontrib><creatorcontrib>Malone, Danielle</creatorcontrib><creatorcontrib>Buoninfante, Alessandra</creatorcontrib><creatorcontrib>Willms, Matthew</creatorcontrib><creatorcontrib>Chan, Rita</creatorcontrib><creatorcontrib>DuMont, Ashley L</creatorcontrib><creatorcontrib>McLahan, Craig</creatorcontrib><creatorcontrib>Grubb, Kaitlyn</creatorcontrib><creatorcontrib>Romanello, Anthony</creatorcontrib><creatorcontrib>van den Dobbelsteen, Germie</creatorcontrib><creatorcontrib>Torres, Victor J</creatorcontrib><creatorcontrib>Poolman, Jan T</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernandez, Jeffrey</au><au>Sanders, Holly</au><au>Henn, Jessica</au><au>Wilson, Jolaine M</au><au>Malone, Danielle</au><au>Buoninfante, Alessandra</au><au>Willms, Matthew</au><au>Chan, Rita</au><au>DuMont, Ashley L</au><au>McLahan, Craig</au><au>Grubb, Kaitlyn</au><au>Romanello, Anthony</au><au>van den Dobbelsteen, Germie</au><au>Torres, Victor J</au><au>Poolman, Jan T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2022-04-19</date><risdate>2022</risdate><volume>225</volume><issue>8</issue><spage>1460</spage><epage>1470</epage><pages>1460-1470</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract
Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.
We developed a robust and translational minipig deep surgical wound infection model to better predict the efficacy of Staphylococcus aureus vaccines in human clinical trials. Leucocidin AB was shown to have potential as a vaccine antigen against S. aureus.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33895843</pmid><doi>10.1093/infdis/jiab219</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2022-04, Vol.225 (8), p.1460-1470 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Bacteria Bacterial Load Bacterial Proteins Clinical trials Leukocidin Leukocidins Major and Brief Reports Staphylococcal Infections - microbiology Staphylococcal Vaccines Staphylococcus aureus Surgical site infections Surgical Wound Infection - prevention & control Swine Swine, Miniature Toxoids Vaccination Vaccines Wound infection |
| title | Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model |
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