A probiotic yeast-based immunotherapy against Clostridioides difficile infection

被引:77
作者
Chen, Kevin [1 ]
Zhu, Yixuan [2 ,4 ]
Zhang, Yongrong [1 ]
Hamza, Therwa [1 ]
Yu, Hua [3 ]
Saint Fleur, Ashley [1 ]
Galen, James [2 ]
Yang, Zhiyong [3 ]
Feng, Hanping [1 ]
机构
[1] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA
[3] FZata Inc, Halethorpe, MD 21227 USA
[4] GeneCopoeia Inc, Rockville, MD 20850 USA
关键词
ANTITOXIN ANTIBODIES ACTOXUMAB; SACCHAROMYCES-BOULARDII; MONOCLONAL-ANTIBODIES; TOXIN-A; FECAL MICROBIOTA; PASSIVE-IMMUNIZATION; GUT MICROBIOTA; TOXOID VACCINE; MOUSE MODEL; IN-VITRO;
D O I
10.1126/scitranslmed.aax4905
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB toxins, the major virulence factors of CDI, represents an effective strategy to combat the disease without invoking antibiotic resistance. However, current antitoxin approaches are mostly based on parenteral infusion of monoclonal antibodies that are costly, narrow spectrum, and not optimized against the intestinal disease. Here, we engineered probiotic Saccharomyces boulardii to constitutively secrete a single tetra-specific antibody that potently and broadly neutralized both toxins and demonstrated protection against primary and recurrent CDI in both prophylactic and therapeutic mouse models of disease. This yeast immunotherapy is orally administered, can be used concurrently with antibiotics, and may have potential as a prophylactic against CDI risk and as a therapeutic for patients with CDI.
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页数:10
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