Nebulization as a delivery method for mAbs in respiratory diseases

Respaud, Renaud; Vecellio, Laurent; Diot, Patrice; Heuzé-Vourc’h, Nathalie

doi:10.1517/17425247.2015.999039

Cited by 117 publications

(115 citation statements)

References 101 publications

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“…With respect to burden of treatment, DPIs give time back to patients when compared to nebulizers, through more rapid administration and delivery, but also additional maintenance time is saved as DPIs do not require as much cleaning as nebulizers . These time‐saving aspects of DPIs are thought to contribute to improved adherence and QoL in patients using these devices . DPIs also prevent loss of the loaded drug upon administration, as compared to most nebulizers .…”

Section: Resultsmentioning

confidence: 99%

“…90 These time-saving aspects of DPIs are thought to contribute to improved adherence and QoL in patients using these devices. 91 DPIs also prevent loss of the loaded drug upon administration, as compared to most nebulizers. 76 Furthermore, there is a limit to the number of capsules constituting a dose and the length of time required for a treatment.…”

Section: Inhalation Drug Delivery Systemsmentioning

confidence: 99%

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Clinical implications ofPseudomonas aeruginosalocation in the lungs of patients with cystic fibrosis

Moore

Mastoridis

2017

J Clin Pharm Ther

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SummaryWhat is known and objective: Pseudomonas aeruginosa is the leading cause of lung infection in patients with cystic fibrosis (CF) and is associated with significant morbidity and mortality. Antibiotics are regarded as the foundational pharmacological treatment for the suppressive management of chronic P. aeruginosa infections and to eradicate the first infection by P. aeruginosa. Inhalation remains a preferred route for drug administration, providing direct access to the site of infection while minimizing systemic side effects. Effective suppressive management of P. aeruginosa infections, however, requires an understanding of the location of the bacteria in the lungs and consideration of the factors that could limit access of the inhaled antibiotic to the infected area. This review provides a systematic assessment of the scientific literature to gain insight into the location of P. aeruginosa in the lungs of patients with CF and its clinical implications. The characteristics of antibiotic inhalation systems are also discussed in this context. Methods:We reviewed evidence-based literature from both human and animal studies in which P. aeruginosa lung location was reported. Relevant publications were identified through a screening strategy and summarized by reported P. aeruginosa location.Results and discussion: Most areas of the conductive and respiratory zones of the lungs are susceptible to P. aeruginosa colonization. Deposition of an inhaled antibiotic is dependent on the device and formulation characteristics, as well as the ability of the patient to generate sufficient inhaled volume. As patients with CF often experience a decline in lung function, the challenge is to ensure that the inhaled antibiotic can be delivered throughout the bronchial tree.

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Section: Resultsmentioning

confidence: 99%

Section: Inhalation Drug Delivery Systemsmentioning

confidence: 99%

Clinical implications ofPseudomonas aeruginosalocation in the lungs of patients with cystic fibrosis

Moore

Mastoridis

2017

J Clin Pharm Ther

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“…In this model, our antibody showed high efficacy both in prophylaxis and therapy, with reduction of lung viral titers of 100-1,000-fold, as well as reduction of signs and pathology. There is increasing evidence that antibodies can be efficiently delivered through nebulization (22)(23)(24). It was interesting to find that when administered intranasally LCA60 was effective in both mouse models and even when tested at concentrations as low as 0.12 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus

Corti

Zhao

Pedotti

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

223

234

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Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.MERS-CoV | neutralizing antibody | serotherapy | emerging viruses

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“…Their advantageous biophysical properties have led to the 58 evaluation of several VHHs as therapeutics against common respiratory pathogens, such as 59 respiratory syncytial virus (RSV) (Detalle et al, 2016;Rossey et al, 2017). The use of VHHs as 60 biologics in the context of a respiratory infection is a particularly attractive application, since the 61 highly stable VHHs can be nebulized and administered via an inhaler directly to the site of 62 infection (Respaud et al, 2015). Moreover, due to their stability after prolonged storage, VHHs 63 could be stockpiled as therapeutic treatment options in case of an epidemic.…”

Section: Introductionmentioning

confidence: 99%

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

Wrapp

Vlieger

Corbett

et al. 2020

Preprint

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ABSTRACTThe pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

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Nebulization as a delivery method for mAbs in respiratory diseases

Cited by 117 publications

References 101 publications

Clinical implications ofPseudomonas aeruginosalocation in the lungs of patients with cystic fibrosis

Clinical implications ofPseudomonas aeruginosalocation in the lungs of patients with cystic fibrosis

Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

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