Inhalation monoclonal antibody therapy: a new way to treat and manage respiratory infections

Abstract

The route of administration of a therapeutic agent has a substantial impact on its success. Therapeutic antibodies are usually administered systemically, either directly by intravenous route, or indirectly by intramuscular or subcutaneous injection. However, treatment of diseases contained within a specific tissue necessitates a better alternate route of administration for targeting localised infections. Inhalation is a promising non-invasive strategy for antibody delivery to treat respiratory maladies because it provides higher concentrations of antibody in the respiratory airways overcoming the constraints of entry through systemic circulation and uncertainity in the amount reaching the target tissue. The nasal drug delivery route is one of the extensively researched modes of administration, and nasal sprays for molecular drugs are deemed successful and are presently commercially marketed. This review highlights the current state and future prospects of inhaled therapies, with an emphasis on the use of monoclonal antibodies for the treatment of respiratory infections, as well as an overview of their importance, practical challenges, and clinical trial outcomes. Key points • Immunologic strategies for preventing mucosal transmission of respiratory pathogens. • Mucosal-mediated immunoprophylaxis could play a major role in COVID-19 prevention. • Applications of monoclonal antibodies in passive immunisation.

Potent universal-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody

“…The ability of 1249A8 given as a single dose to mitigate SARS-CoV-2 pathology and viral burden against all VoC tested when used either prophylactically or therapeutically, along with the added benefit of combining with a broad and potent RBD-specific hmAb substantiate its clinical potential. Further we demonstrated that direct respiratory delivery of hmAb results in potent in vivo activity, consistent with our and others previous finding of its more rapid and efficient distribution of mAb to the airways compared to systemic administration(16, 34). The demonstrated activity of 1249A8 against all β-CoV further highlights its clinical potential against future SARS-CoV-2 VoCs, novel β-CoVs, as well as seasonal β-CoV.…”

Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody

“…The ability of 1249A8 given as a single dose to mitigate SARS-CoV-2 pathology and viral burden against all VoC tested when used either prophylactically or therapeutically, along with the added benefit of combining with a broad and potent RBD-specific hmAb substantiate its clinical potential. Further we demonstrated that direct respiratory delivery of hmAb results in potent in vivo activity, consistent with our and others previous finding of its more rapid and efficient distribution of mAb to the airways compared to systemic administration [ 18 , 36 ]. The demonstrated activity of 1249A8 against all β-CoV further highlights its clinical potential against future SARS-CoV-2 VoCs, novel β-CoVs, as well as seasonal β-CoV.…”

ERS International Congress 2021: highlights from the Respiratory Infections Assembly

“…Several studies emphasised host-directed therapy, targeting host immune and inflammatory pathways to enhance immune response that could improve treatment outcomes in patients with infectious diseases. This has been confirmed by research on corticosteroids usage in COVID-19 pneumonia [ 47 ], macrolides in bronchiectasis [ 67 ], and monoclonal antibody-based therapies [ 68 – 70 ]. Recombinant human plasma has also shown promise in improving survival and attenuating lung injury [ 71 , 72 ] with low propensity for resistance [ 73 ].…”