{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:04:13Z","timestamp":1792260253786,"version":"4.4.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The increase in urinary tract infections (UTI) caused by antibiotic-resistant\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR)\n                      <jats:italic>E. coli<\/jats:italic>\n                      serotype O25b ST131 isolate.\n                      <jats:italic>E. coli<\/jats:italic>\n                      fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively. Accordingly, we assessed the protective efficacy of three 50-\u00b5g intramuscular doses of a novel recombinant FimH antigen adjuvanted with liposomal QS21\/MPLA compared with saline placebo in groups of nine animals. A third group was vaccinated with this FimH formulation in combination with 1 \u00b5g each of a four-valent mixture of serotype O1a, O2, O6, and O25b O-antigen CRM\n                      <jats:sub>197<\/jats:sub>\n                      lattice glycoconjugates. Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination group, O-antigen-specific antibodies. Following bacterial challenge, both vaccinated groups showed &gt;200- and &gt;700-fold reduction in bacteriuria at day 2 and day 7 post-infection compared with placebo, respectively. In parallel, both vaccines significantly reduced levels of inflammatory biomarkers IL-8 and myeloperoxidase in the urine at day 2 post-infection relative to placebo. Results provide preclinical proof-of-concept for the prevention of an MDR UTI infection by these new vaccine formulations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00169-24","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T09:04:39Z","timestamp":1726736679000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["A cynomolgus monkey\n                    <i>E. coli<\/i>\n                    urinary tract infection model confirms efficacy of new FimH vaccine candidates"],"prefix":"10.1128","volume":"92","author":[{"given":"Laurent","family":"Chorro","sequence":"first","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Ciolino","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caresse Lynn","family":"Torres","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Illenberger","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JohnPaul","family":"Aglione","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Corts","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Lypowy","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ponce","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalena","family":"La Porte","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Burt","sequence":"additional","affiliation":[{"name":"Pfizer Drug Safety Research and Development, Groton, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen L.","family":"Volberg","sequence":"additional","affiliation":[{"name":"Pfizer Drug Safety Research and Development, Groton, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"Pfizer Drug Safety Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"McGovern","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Hu","sequence":"additional","affiliation":[{"name":"Pfizer Research Biostatistics, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annaliesa S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie C.","family":"Silmon de Monerri","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis","family":"Kanevsky","sequence":"additional","affiliation":[{"name":"Pfizer Vaccine Research and Development, Pearl River, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1002-954X","authenticated-orcid":true,"given":"Robert G. 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