{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:34:23Z","timestamp":1792798463868,"version":"4.5.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The Ministry of Science and Technology of China, National Key R&D Program of China","award":["2018YFA0903100"],"award-info":[{"award-number":["2018YFA0903100"]}]},{"name":"Shenzhen Medical Academy of Research and Translation fundings","award":["B2302023, A2303035"],"award-info":[{"award-number":["B2302023, A2303035"]}],"id":[{"id":"https:\/\/ror.org\/00jsay989","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shenzhen Institute of Synthetic Biology Scientific Research Program","award":["JCHZ20200001"],"award-info":[{"award-number":["JCHZ20200001"]}],"id":[{"id":"https:\/\/ror.org\/058rt6c45","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32001038"],"award-info":[{"award-number":["32001038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Outstanding Scientific Innovation Talents Training Project","award":["RCBS20210706092214015"],"award-info":[{"award-number":["RCBS20210706092214015"]}]},{"name":"Programs Foundation of 20 articles for colleges and universities in Jinan","award":["2020GXRC026"],"award-info":[{"award-number":["2020GXRC026"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,1,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage\u2013body interactions has limited its clinical application. Here, we administered different purified phages (\n                    <jats:italic>Salmonella<\/jats:italic>\n                    phage SE_SZW1,\n                    <jats:italic>Acinetobacter<\/jats:italic>\n                    phage AB_SZ6, and\n                    <jats:italic>Pseudomonas<\/jats:italic>\n                    phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2\u20133 Log\n                    <jats:sub>10<\/jats:sub>\n                    decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Phage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage\u2013host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage\u2013host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01359-23","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T09:00:26Z","timestamp":1702371626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Evaluation of the impact of repeated intravenous phage doses on mammalian host\u2013phage interactions"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2705-4613","authenticated-orcid":false,"given":"Xin","family":"Tan","sequence":"first","affiliation":[{"name":"Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"New Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences, Shandong Academy of Pharmaceutical Sciences, Jinan, China"},{"name":"Shandong Innovation Center of Engineered Bacteriophage Therapeutics, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"New Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences, Shandong Academy of Pharmaceutical Sciences, Jinan, China"},{"name":"Shandong Innovation Center of Engineered Bacteriophage Therapeutics, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced 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