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: When splenocytes from naïve or immunized mice were exposed to native or PEGylated phages, antigen‐specific T‐cell proliferation was observed 3 days after antigen treatment. The formation of blasts which accompanied the proliferation of activated T cells was monitored by light microscopy. No stimulation was observed in the control, confirming antigen‐specific cell proliferation upon bacteriophage presentation. After initiation, tritium‐labelled thymidine was added, and radioactivity was measured after 20 h incubation (Fig. 6). For Felix‐O1, the stimulation indices in splenocytes from naïve mice were 4.4 ± 0.8 (PBS–WT) and 1.4 ± 0.3 (PBS–PEG), while in those from immunized mice, it was 7.4 ± 1.6 (WT–WT) and 2.3 ± 0.3 (PEG–PEG).
Affiliation: Institute of Food Science and Nutrition, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.