Respirable Bacteriophage Aerosols for the Prevention and Treatment of Tuberculosis

Hatfull, Graham F.; Vehring, Reinhard

doi:10.1002/9781118943182.ch14

Cited by 9 publications

(12 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The development of regulatory-approved, commercial phage formulations for inhalation will likely require the use of cocktails containing various phages that target different receptors to ensure that M. tuberculosis does not become phage resistant (17). The development of anti-TB cocktails is an active area of research (17). Phage D29 and others that may be included in a therapeutic cocktail would be applicable for the prevention of drug-sensitive or drug-resistant strains of M. tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, antibiotic resistance does not influence bacterial susceptibility to phage lysis (16), making phages an attractive tool against drug-resistant organisms. Phages predicted to use obligatory lytic life cycles can be distinguished from temperate phages through genetic analysis (17). The lytic cycle encompasses the injection of phage DNA into the cell, phage replication, and lysis of the bacterial cell wall to release the progeny.…”

mentioning

confidence: 99%

“…Note that phage aerosol delivery without the use of additional vectors is unlikely to have efficacy against M. tuberculosis already harbored within a granuloma; even phage infection of M. tuberculosis within a macrophage, the primary target cell of M. tuberculosis, has low efficiency (33). However, prophylactic delivery of phages to the alveoli may allow the phage to infect the mycobacteria before macrophage uptake (17,27,34). Since the lungs contain millions of alveoli, a high dose of active phage is likely required for prophylaxis.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

Carrigy

Larsen

Reese

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Globally, more people die annually from tuberculosis than from any other single infectious agent. Unfortunately, there is no commercially available vaccine that is sufficiently effective at preventing the acquisition of pulmonary tuberculosis in adults. In this study, preexposure prophylactic pulmonary delivery of active aerosolized antituberculosis bacteriophage D29 was evaluated as an option for protection against Mycobacterium tuberculosis infection. An average bacteriophage concentration of approximately 1 PFU/alveolus was achieved in the lungs of mice using a nose-only inhalation device optimized with a dose simulation technique and adapted for use with a vibrating mesh nebulizer. Within 30 min of bacteriophage delivery, the mice received either a low dose (∼50 to 100 CFU) or an ultralow dose (∼5 to 10 CFU) of M. tuberculosis H37Rv aerosol to the lungs. A prophylactic effect was observed, with bacteriophage aerosol pretreatment significantly decreasing M. tuberculosis burden in mouse lungs at 24 h and 3 weeks postchallenge (P < 0.05). These novel results indicate that a sufficient dose of nebulized mycobacteriophage aerosol to the lungs may be a valuable intervention to provide extra protection to health care professionals and other individuals at risk of exposure to M. tuberculosis.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

Carrigy

Larsen

Reese

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…Phages present an alternative resource in combating bacteria-related diseases (Kutateladze and Adamia, 2010). Phages are viruses that infect bacteria and can have a narrow host range of target bacteria (Hatful and Vehring, 2016; Dewangan et al, 2017). This narrow host range results in little to no off target effects, unlike what is seen with conventional antibiotics which often damage microbiota (Loc-Carrillo and Abedon, 2011; Dewangan et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…There are many phages with varying structures, one of which consists of a polyhedral capsid containing genetic material and a tail used to bind to the bacteria and inject the genetic material (Hatful and Vehring, 2016; Dewangan et al, 2017). Although not all phages can be used as therapeutic agents, lytic phages tend to be the most useful, due to their exponential growth and effectiveness in eradicating the host bacteria (Kutateladze and Adamia, 2010).…”

Section: Introductionmentioning

confidence: 99%

Atmospheric Spray Freeze Drying of Sugar Solution With Phage D29

Carrigy

Wang

et al. 2019

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

Therapeutic bacteriophages offer a potential alternative approach in the treatment of drug resistant bacteria. In the present study, we examine the ability of atmospheric spray freeze-drying (ASFD) to process bacteriophage D29 into a solid dry formulation. Bacteriophage D29 is of particular interest due to its ability to infect Mycobacterium tuberculosis . A sugar solution containing bacteriophage D29 was sprayed and instantly frozen in a cold chamber. Cold drying gas was then passed through the chamber at a high flow rate and atmospheric pressure. Convective transport combined with the low temperature of the drying gas results in sublimation of ice, yielding a free-flowing, porous powder. The bacteriophages were atmospheric spray freeze-dried in solutions with varying concentrations of trehalose and mannitol. A solution of trehalose and mannitol at a mass ratio of 7:3 and a total mass concentration of 100 mg/mL led to powder with 4.9 ± 0.1% moisture content and an acceptable titer reduction of ∼0.6 logs. In comparison, a pure trehalose solution and a 1:1 ratio of trehalose and mannitol both had titer reductions of >1.5 logs. Spectroscopic analysis showed that trehalose in the powder was amorphous while mannitol completely crystallized during the drying process, both of which are desirable for preserving phage viability and storage in powders. The results highlight the potential for using ASFD as an alternative process in preserving biopharmaceutical products.

show abstract

Effect of storage temperature on the stability of spray dried bacteriophage powders

Leung

Parumasivam

Nguyen

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

Self Cite

View full text Add to dashboard Cite

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 10 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 10-10 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.

show abstract

Respirable Bacteriophage Aerosols for the Prevention and Treatment of Tuberculosis

Cited by 9 publications

References 71 publications

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

Atmospheric Spray Freeze Drying of Sugar Solution With Phage D29

Effect of storage temperature on the stability of spray dried bacteriophage powders

Contact Info

Product

Resources

About