Bacteriophage Ecology
Population Growth, Evolution, and Impact of Bacterial Viruses
EDITED BY
STEPHEN T. ABEDON
Chapter 13
Interaction of bacteriophages with animals (Carl R. Merril)
“13.3 THE FATE OF PHAGES ADMINISTERED TO ANIMALS
...Rapid elimination of phages from the circulatory system is due to functions associated with the organs of the reticulo-endothelial system, primarily the liver and spleen.”
“13.3.1 Phage interactions with the adaptive immune system
When a specific phage strain is first inoculated into an animal or human, if there are no detectable pre-existing antibodies for that specific phage strain, then it is defined as a neoantigen. Whether a phage strain serves as a neoantigen within a given individual depends on the phage-exposure and physiological history of that individual.
...The presence of adaptive antibodies can have significant effects on the pharmacokinetics of phage experiments and/or therapy.”
“13.3.3 Fate of orally administered phages
It should be noted that some investigators who have administered phages orally report the subsequent detection of phages in the circulatory system (Dabrowska et al., 2005a; Görski et al., 2006). While these findings are compatible with the finding of a trace amount of phage in the spleen, liver, and kidney in the germ-free animal experiments, it may be difficult, as previously noted (Section 13.3.2), to achieve the titers needed for some acute infection therapies by the oral route. This concern with limitations of oral phage administration was reinforced by the observations that when healthy adult volunteers were administered T4 phage in their drinking water ,neither T4 phages nor T4-specific antibodies were found in the serum of the volunteers by the end of the study (Bruttin and Brüssow, 2005)”.
From:
BACTERIOPHAGES Biology and Applications
EDITED BY
Elizabeth Kutter
Alexander Sulakvelidze
Chapter 14
Bacteriophage Therapy in Humans
14.5.2.3. The Development of Phage-Neutralizing Antibodies
“...various parameters affect the development of phage neutralizing antibodies. Levels of phage-neutralizing antibodies are low after a single injection or after a series of closely spaced injections, and most of the antibody that develops under these regimes is of the IgM type, whose neutralizing activity is low and largely reversible (Gachechiladze, Chapter 3 box and personal communication).
High titers of long-lasting, higher-affinity IgG antibodies are seen only when multiple injections are spaced several weeks apart. Thus, the production of neutralizing antibodies (i. e., antibodies against the tail adhesins) should not be a significant obstacle during initial or relatively short-term therapeutic treatments, at least. Furthermore,the antigenic properties vary considerably between different phage families; for example, T4 phage is a good immunogen, but T1 and T5 phages are much less antigenic, and a Bacillus subtilis phage reportedly needs an adjuvant and repeated intraperitoneal injections to generate a detectable immune response (Adams, 1959a).”
14.5.2.1. Phage Movement between Biological Compartments
“Indeed, more recent reports have shown that in the presence of host bacteria, therapeutic phages can be found in the mammalian circulatory system irrespective of the administration route; e.g., therapeutic phages administered orally to infected patients were recoverable from their bloodstream for several days (Babalova et al., 1968; Weber-Dabrowska et al., 1987). Also, studies with experimentally infected animals (Bogovazova et al.,1991; 1992) found that phages enter the bloodstream within 2 to 4 hours, and that they are still recoverable from the internal organs (liver, spleen, kidney, etc.) after ca. 10 hours postinjection.”
