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The Hemagglutinin A Stem Antibody MEDI8852 Prevents and Controls Disease and Limits Transmission of Pandemic Influenza Viruses
- Source :
- The Journal of Infectious Diseases. 216:356-365
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Background MEDI8852 is a novel monoclonal antibody (mAb) that neutralizes both group I and group II influenza A viruses (IAVs) in vitro. We evaluated whether MEDI8852 was effective for prophylaxis and therapy against representative group I (H5N1) and group II (H7N9) pandemic IAVs in mice and ferrets and could be used to block transmission of influenza H1N1pdm09 in ferrets, compared to an irrelevant control mAb R347 and oseltamivir. Methods MEDI8852 was administered to mice and ferrets by intraperitoneal injection at varying doses, 24 hours prior to intranasal infection with H5N1 and H7N9 viruses for prophylaxis, and 24, 48, and 72 hours post-infection for treatment. A comparison with oseltamivir alone and combination of MEDI8852 and oseltamivir was included in some studies. Survival, weight loss, and viral titers were assessed over a 14-day study period. For the transmission study, naive respiratory contact ferrets received MEDI8852 or R347 prior to exposure to ferrets infected with an H1N1pdm09 virus. Results MEDI8852 was effective for prophylaxis and treatment of H7N9 and H5N1 infection in mice, with a clear dose-dependent response and treatment with MEDI8852 24, 48, or 72 hours postinfection was superior to oseltamivir for H5N1. MEDI8852 alone was effective treatment for lethal H5N1 infection in ferrets compared to oseltamivir and R347, and MEDI8852 plus oseltamivir was better than oseltamivir alone. MEDI8852 or oseltamivir alone early in infection was equally effective for H7N9 infection in ferrets while the combination yielded similar protection when treatment was delayed. MEDI8852 was able to protect naive ferrets from airborne transmission of H1N1pdm09. Conclusions MEDI8852, alone or with oseltamivir, shows promise for prophylaxis or therapy of group I and II IAVs with pandemic potential. Additionally, MEDI8852 blocked influenza transmission in ferrets, a unique finding among influenza-specific mAbs.
- Subjects :
- 0301 basic medicine
Oseltamivir
viruses
Hemagglutinin (influenza)
Antibodies, Monoclonal, Humanized
Antibodies, Viral
Influenza A Virus, H7N9 Subtype
medicine.disease_cause
Antiviral Agents
Airborne transmission
H5N1 genetic structure
Virus
Major Articles
Mice
03 medical and health sciences
chemistry.chemical_compound
Orthomyxoviridae Infections
Antibody Specificity
Influenza A virus
Animals
Humans
Immunology and Allergy
Medicine
Mice, Inbred BALB C
Influenza A Virus, H5N1 Subtype
biology
business.industry
Ferrets
Antibodies, Monoclonal
virus diseases
Antibodies, Neutralizing
Virology
Influenza A virus subtype H5N1
030104 developmental biology
Infectious Diseases
chemistry
biology.protein
Female
Antibody
business
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 216
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....a3635cb391d188dd077e785bf1ba9a20