Anti-phage аntibody response in phage therapy against healthcare-associated infections (HAIs)

Bochkareva, S.S.; Aleshkin, A. V.; Ershova, Olga; Новикова, Л. Ю.; Karaulov, Alexander; Киселева, И. А.; Zul'karneev, E R; Rubal’skiy, E.O.; Zeigarnik, M.V.

doi:10.20953/1729-9225-2017-1-35-40

Cited by 15 publications

(13 citation statements)

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“…The authors stated that repeated doses of phages do not eradicate infection more efficiently than the single dose and suggest that repeated doses have undesired consequences, such as the development of anti-phage antibodies. A change in the composition of the phage strains is required for future treatments (125). In another study from Russia, 14 patients with MDR A. baumannii, K. pneumoniae, P. aeruginosa, and S. aureus growth in several samples, including endotracheal aspirate, blood, and urine, had a microbiologic response to a 3-day phage therapy (126).…”

Section: New Therapeutic Optionsmentioning

confidence: 99%

“…Schooley et al administered phages through intracystic, intraabdominal, and intravenous routes, whereas Russian researchers used gastrointestinal (oral and intragastric) and endotracheal routes. There are not clearly defined dosing intervals currently, and unfavorable outcomes of multiple dosing may occur (125). It is necessary to detect anti-phage antibodies for a customized therapy with repeated doses.…”

Section: New Therapeutic Optionsmentioning

confidence: 99%

“…Another handicap of this therapeutic option is resistance as shown by Schooley et al, where one of the strains developed resistance to the bacteriophage cocktail 8 days after the initiation of therapy (122). This may in part be overcome with the development of new phages against the new resistant strain, which requires an active "on-demand" service for the rapid selection of new phage strains (125).…”

Section: New Therapeutic Optionsmentioning

confidence: 99%

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New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

252

179

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Carbapenem-resistantAcinetobacter baumannii(CRAB) is a perilous nosocomial pathogen causing substantial morbidity and mortality. Current treatment options for CRAB are limited and suffer from pharmacokinetic limitations, such as high toxicity and low plasma levels. As a result, CRAB is declared as the top priority pathogen by the World Health Organization for the investment in new drugs. This urgent need for new therapies, in combination with faster FDA approval process, accelerated new drug development and placed several drug candidates in the pipeline. This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late-stage preclinical studies for the treatment of CRAB, and it evaluates their expected benefits and potential shortcomings.

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Section: New Therapeutic Optionsmentioning

confidence: 99%

Section: New Therapeutic Optionsmentioning

confidence: 99%

Section: New Therapeutic Optionsmentioning

confidence: 99%

See 1 more Smart Citation

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Isler¹,

Doi

Bonomo

et al. 2019

Antimicrob Agents Chemother

252

179

View full text Add to dashboard Cite

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“…Although the stimulating effect of bacteriophages on the immune system, shown in experiments in vivo and in vitro is known from the literature [4,8,10, 15], the changes that we observed in the immune status of patients after phage therapy would probably be more correctly regarded as not immunostimulation, but redistribution of lymphocytes between individual sites of the immune system.…”

Section: Resultsmentioning

confidence: 70%

Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

et al. 2021

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Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued.

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“…Factors determining these interactions are unclear; however, phage-specific antibodies are of significant concern because they can influence phage infectivity by neutralization and Fc-dependent and complement-dependent phagocytosis [ 9 , 10 ]. Although anti-phage antibodies have been widely shown, their influence on therapy is unforeseen, demonstrating both worsening [ 11 , 12 ] and neutral [ 13 ] effects.…”

Section: Introductionmentioning

confidence: 99%

Influence of Caudovirales Phages on Humoral Immunity in Mice

Чечушков

Kozlova

Baykov

et al. 2021

Viruses

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Bacteriophages are promising antibacterial agents. Although they have been recognized as bacterial viruses and are considered to be non-interacting with eukaryotic cells, there is growing evidence that phages may have a significant impact on the immune system via interactions with macrophages, neutrophils, and T-cell polarization. In this study, the influence of phages of podovirus, siphovirus, and myovirus morphotypes on humoral immunity of CD-1 mice was investigated. In addition, tissue distribution of the phages was tested in these mice. No common patterns were found either in the distribution of phages in mice or in changes in the levels of cytokines in the sera of mice once injected with phages. Importantly, pre-existing IgM-class antibodies directed against capsid proteins of phages with myovirus and siphovirus morphotypes were identified in mice before immunization. After triple immunization of CD1-mice with phages without any adjuvant, levels of anti-phage serum polyclonal IgG antibodies increased. Immunogenic phage proteins recognized by IgM and/or IgG antibodies were identified using Western blot analysis and mass spectrometry. In addition, mice serum collected after immunization demonstrated neutralizing properties, leading to a substantial decrease in infectivity of investigated phages with myovirus and siphovirus morphotypes. Moreover, serum samples collected before administration of these phages exhibited some ability to reduce the phage infectivity. Furthermore, Proteus phage PM16 with podovirus morphotype did not elicit IgM or IgG antibodies in immunized mice, and no neutralizing activities against PM16 were revealed in mouse serum samples before and after immunization.

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Anti-phage аntibody response in phage therapy against healthcare-associated infections (HAIs)

Cited by 15 publications

References 0 publications

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

Influence of Caudovirales Phages on Humoral Immunity in Mice

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