In Vivo Assessment of Antibody-Dependent Enhancement of Influenza B Infection

Toxicological Sciences : an Official Journal of the Society of Toxicology
Gautham K RaoWendy G Halpern

Abstract

A theoretical safety concern proposed in the influenza literature is that therapeutic antiviral antibodies could have the potential for antibody-dependent enhancement (ADE) of infection and disease. ADE may occur when virus-specific antibodies at subtherapeutic, nonneutralizing concentrations facilitate virus uptake and, in some cases, enhance replication, which can lead to an exacerbation of virus-mediated disease. Alternatively, ADE may occur due to antibody-dependent complement activation exacerbating virus-mediated disease in the absence of increased replication. As a result of this theoretical safety concern, safety assessment of anti-influenza antibodies may include an in vivo evaluation of ADE of infection and/or disease. These studies were conducted to investigate the potential of MHAB5553A, a broadly specific, neutralizing therapeutic anti-influenza B antibody, to elicit ADE of infection and disease in mouse models of influenza B infection. In parallel studies, female DBA/2J mice were infected with either influenza B/Victoria/504/2000 or influenza B/Brisbane/60/2008 representing distinct lineages. Assessment of ADE was based on an integration of results from multiple endpoints, including infectious lung viral titers an...Continue Reading

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Citations

Aug 13, 2020·Nature Reviews. Immunology·Stylianos BournazosJeffrey V Ravetch
Nov 30, 2021·Pediatric Pulmonology·Arindam ChakrabartiUNKNOWN Pediatric Intensive Care Influenza (PICFLU) Investigators

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