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PEGylation of bacteriophages increases blood circulation time and reduces T-helper type 1 immune response.

Kim KP, Cha JD, Jang EH, Klumpp J, Hagens S, Hardt WD, Lee KY, Loessner MJ - Microb Biotechnol (2008)

Bottom Line: When injected into naïve mice, PEGylated phages showed a strong increase in circulation half-life, whereas challenge of immunized mice did not reveal a significant difference.Our results suggest that the prolonged half-life is due to decreased susceptibility to innate immunity as well as avoidance of cellular defence mechanisms.PEGylated viruses elicited significantly reduced levels of T-helper type 1-associated cytokine release (IFN-γ and IL-6), in both naïve and immunized mice.

View Article: PubMed Central - PubMed

Affiliation: Institute of Food Science and Nutrition, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.

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Phage inactivation in the presence of innate immunity in the mouse model, both in vivo for A511 (A) and Felix‐O1 (B), and in vitro (C). In (C), 0, 1, 2 and 4 indicate the incubation time in the presence of serum. In in vivo studies, the number of phage per 5 µl at 0 h is represented as 100%, corresponded to 1 × 106 PFU for WT A511 and 1 × 105 PFU for PEGylated A511, and 1 × 106 PFU for WT Felix‐O1 and 3 × 105 PFU for PEGylated Felix‐O1. The asterisk (*) denotes statistical significance (α = 0.05).
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f3: Phage inactivation in the presence of innate immunity in the mouse model, both in vivo for A511 (A) and Felix‐O1 (B), and in vitro (C). In (C), 0, 1, 2 and 4 indicate the incubation time in the presence of serum. In in vivo studies, the number of phage per 5 µl at 0 h is represented as 100%, corresponded to 1 × 106 PFU for WT A511 and 1 × 105 PFU for PEGylated A511, and 1 × 106 PFU for WT Felix‐O1 and 3 × 105 PFU for PEGylated Felix‐O1. The asterisk (*) denotes statistical significance (α = 0.05).

Mentions: The proportion of infective A511‐wt particles in the mouse blood circulation dropped rapidly; only 3.3% of the initial PFUs remained 1.5 h after injection (Fig. 3A). The decrease continued further; we measured 0.016% residual infectivity 6 h post injection, and 0.001% infective particles 24 h after injection. In contrast, PEGylated A511‐PEG phages survived much better; 83.7% and 20.9% of the PFUs remained after 1.5 and 6 h injection respectively (Fig. 3A). The A511‐PEG clearance followed an almost linear function, with 0.01% infectivity remaining after 24 h incubation (Fig. 3A). At 6 h post injection, the difference between native and PEGylated phage reached a maximum of more than 3 logs.


PEGylation of bacteriophages increases blood circulation time and reduces T-helper type 1 immune response.

Kim KP, Cha JD, Jang EH, Klumpp J, Hagens S, Hardt WD, Lee KY, Loessner MJ - Microb Biotechnol (2008)

Phage inactivation in the presence of innate immunity in the mouse model, both in vivo for A511 (A) and Felix‐O1 (B), and in vitro (C). In (C), 0, 1, 2 and 4 indicate the incubation time in the presence of serum. In in vivo studies, the number of phage per 5 µl at 0 h is represented as 100%, corresponded to 1 × 106 PFU for WT A511 and 1 × 105 PFU for PEGylated A511, and 1 × 106 PFU for WT Felix‐O1 and 3 × 105 PFU for PEGylated Felix‐O1. The asterisk (*) denotes statistical significance (α = 0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815886&req=5

f3: Phage inactivation in the presence of innate immunity in the mouse model, both in vivo for A511 (A) and Felix‐O1 (B), and in vitro (C). In (C), 0, 1, 2 and 4 indicate the incubation time in the presence of serum. In in vivo studies, the number of phage per 5 µl at 0 h is represented as 100%, corresponded to 1 × 106 PFU for WT A511 and 1 × 105 PFU for PEGylated A511, and 1 × 106 PFU for WT Felix‐O1 and 3 × 105 PFU for PEGylated Felix‐O1. The asterisk (*) denotes statistical significance (α = 0.05).
Mentions: The proportion of infective A511‐wt particles in the mouse blood circulation dropped rapidly; only 3.3% of the initial PFUs remained 1.5 h after injection (Fig. 3A). The decrease continued further; we measured 0.016% residual infectivity 6 h post injection, and 0.001% infective particles 24 h after injection. In contrast, PEGylated A511‐PEG phages survived much better; 83.7% and 20.9% of the PFUs remained after 1.5 and 6 h injection respectively (Fig. 3A). The A511‐PEG clearance followed an almost linear function, with 0.01% infectivity remaining after 24 h incubation (Fig. 3A). At 6 h post injection, the difference between native and PEGylated phage reached a maximum of more than 3 logs.

Bottom Line: When injected into naïve mice, PEGylated phages showed a strong increase in circulation half-life, whereas challenge of immunized mice did not reveal a significant difference.Our results suggest that the prolonged half-life is due to decreased susceptibility to innate immunity as well as avoidance of cellular defence mechanisms.PEGylated viruses elicited significantly reduced levels of T-helper type 1-associated cytokine release (IFN-γ and IL-6), in both naïve and immunized mice.

View Article: PubMed Central - PubMed

Affiliation: Institute of Food Science and Nutrition, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.

Show MeSH
Related in: MedlinePlus