Immunological considerations for developing antibody therapeutics for Influenza A

Human Vaccines & Immunotherapeutics
Po-Ying Chan-Hui, Kristine M Swiderek

Abstract

Influenza infection can give rise to serious illness leading to complications and hospitalization of patients. The efficacy of current standard of care is very limited and provides little relief for patients hospitalized with serious flu. Human monoclonal antibodies (mAb) against influenza are being developed as new treatment options for this patient population. When developing antibody therapeutics, it is important to consider all possible immunologic effects of the antibodies on viral infection and disease progression including those other than the postulated therapeutic mechanisms. An area of concern is the potential of antibody-dependent enhancement (ADE) of illness. ADE of viral infections has been extensively described for Dengue virus (DENV) but not for influenza. Recently, preliminary results from clinical viral challenge studies of anti-HA-stalk mAbs suggested the possibility of enhanced viral shedding, raising concerns for ADE when utilizing mAbs as therapeutic intervention for influenza although viral shedding was not enhanced in the clinical viral challenge of anti-M2 mAb TCN-032. We herein discuss the known mechanisms of ADE and their relevance to developing mAbs such as anti-HA and anti-M2 for influenza disease.

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Citations

Nov 18, 2016·Virologica Sinica·Xiaojing PangGong Cheng
Feb 24, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Gautham K RaoWendy G Halpern
Jul 13, 2018·BioMed Research International·Urai Chaisri, Wanpen Chaicumpa
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Nov 25, 2020·Current Microbiology·Puneet BhattGovindakarnavar Arunkumar

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Clinical Trials Mentioned

NCT01719874
NCT01938352
NCT02468115
NCT02293863

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