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Antimicrob Agents Chemother. 2015 May 4. pii: AAC.00290-15. [Epub ahead of print]
Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza monoclonal antibodies.
Leyva-Grado VH1, Tan GS2, Leon PE3, Yondola M2, Palese P4.
Author information
Abstract
The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective, constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutics that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (mAb) has been sought as an alternative immunotherapy against influenza infection. Here, we tested in mice previously characterized broadly neutralizing anti-HA stalk mAb prophylactically and therapeutically using different routes of administration. Efficacy of treatment against influenza H1N1 pandemic virus challenge was compared between two systemic routes of administration, intraperitoneal (IP) and intravenous (IV) versus two local routes intranasal (IN) and by aerosol (AE). The dose of mAb required for prophylactic protection was reduced by 10-fold in animals treated locally (IN or AE) compared with those treated systemically (IP or IV). Improved therapeutic protection was observed in animals treated IN on day 5 post-infection (60% survival) compared with the IP route (20% survival). An increase in therapeutic efficacy was also observed against other influenza virus subtypes (H5N1) when a local route of administration was used. Our findings demonstrate that local administration significantly decreases the amount of broadly neutralizing monoclonal antibody required for protection against influenza, which highlights the potential use of mAb as a therapeutic for influenza-associated disease.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25941218 [PubMed - as supplied by publisher]
Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza monoclonal antibodies.
Leyva-Grado VH1, Tan GS2, Leon PE3, Yondola M2, Palese P4.
Author information
Abstract
The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective, constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutics that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (mAb) has been sought as an alternative immunotherapy against influenza infection. Here, we tested in mice previously characterized broadly neutralizing anti-HA stalk mAb prophylactically and therapeutically using different routes of administration. Efficacy of treatment against influenza H1N1 pandemic virus challenge was compared between two systemic routes of administration, intraperitoneal (IP) and intravenous (IV) versus two local routes intranasal (IN) and by aerosol (AE). The dose of mAb required for prophylactic protection was reduced by 10-fold in animals treated locally (IN or AE) compared with those treated systemically (IP or IV). Improved therapeutic protection was observed in animals treated IN on day 5 post-infection (60% survival) compared with the IP route (20% survival). An increase in therapeutic efficacy was also observed against other influenza virus subtypes (H5N1) when a local route of administration was used. Our findings demonstrate that local administration significantly decreases the amount of broadly neutralizing monoclonal antibody required for protection against influenza, which highlights the potential use of mAb as a therapeutic for influenza-associated disease.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25941218 [PubMed - as supplied by publisher]