The Hemagglutinin A Stem Antibody MEDI8852 Prevents and Controls Disease and Limits Transmission of Pandemic Influenza Viruses.

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.

• Authors: Catharine I Paules, Seema Lakdawala, Josephine M McAuliffe, Myeisha Paskel, Leatrice Vogel, Nicole L Kallewaard, Qing Zhu, Kanta Subbarao
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 216 Issue 3 Pg. 356-365 (08 01 2017) ISSN: 1537-6613 [Electronic] United States
• PMID: 28633457 (Publication Type: Journal Article)
• Copyright: Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Antibodies, Viral
• Antiviral Agents
• MED18852
• Oseltamivir

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing (administration & dosage)
• Antibodies, Viral (administration & dosage)
• Antibody Specificity
• Antiviral Agents (therapeutic use)
• Female
• Ferrets
• Humans
• Influenza A Virus, H5N1 Subtype
• Influenza A Virus, H7N9 Subtype
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (immunology, prevention & control)
• Oseltamivir (therapeutic use)