These authors have contributed equally to this work

## **References**

Quality control of phage therapy based on Western medicine criteria has to be met. A small scale and strict quality control of a phage cocktail for treatment of *P. aeruginosa* and *S. aureus* infections was conducted in Belgium that included sequencing of whole phage genomes to verify the lack of toxin-encoding genes, confirmation of lytic phage property, lack of temperate phage, stability, removal of pyrogen, sterility and cytotoxicity [126]. This small-scale pilot study may set a foundation of standard in the Western countries for large-scale controlled clinical trials for phage therapy. Phage engineering can be employed to keep bacterial killing property but bypass lysis induced endotoxin release and related side effect [127]. More recently, human humoral immune response against phage therapy showed that anti-phage antibodies (Abs), including IgM, IgG and IgA, were detected in patient sera when staphylococcal MS-1 phage cocktail was used for treatment [128]. Interestingly, these anti-phage Abs

However, it seems that big pharmaceuticals are currently not interested in phage therapy, investment cost burden and patent filing may be another key considerations besides safety concern. To remove the worries from live virus-based therapy, phage-derived proteins (VAPGHs and endolysins) may become an option as these proteins also show the specificity and lytic efficiency against Gram-positive bacteria, albeit less efficient against Gram-negative

DW conceived the topic of the study. All authors wrote the manuscript. LJ and AS contributed

This work was supported by National Natural Science Foundation of China (Grant No.:

and Donghui Wu#,

Laboratory of Antibody Engineering, Shanghai Institute for Advanced Immunochemical

\*

did not compromise the final efficacy [128].

bacteria due to the presence of OM cell wall.

, Abhishek Saxena#

Studies, ShanghaiTech University, Shanghai, China

These authors have contributed equally to this work

\*Address all correspondence to: wudh@shanghaitech.edu.cn

equally in writing the manuscript. DW revised the manuscript.

**Author contributions**

244 Physiology and Pathology of Immunology

**Funding**

81572698) to DW.

**Author details**

Lianlian Jiang#

#


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