PEGylation of bacteriophages increases blood circulation time and reduces T-helper type 1 immune response.
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.
Affiliation: Institute of Food Science and Nutrition, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.Show MeSH
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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.
Affiliation: Institute of Food Science and Nutrition, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.