Passive immunization for influenza through antibody therapies, a review of the pipeline, challenges and potential applications

Abstract

The Global Action Plan for influenza vaccines (GAP) aims to increase the production capacity of vaccines so that in the event of a pandemic there is an adequate supply to meet global needs. However, it has been estimated that even in the best case scenario there would be a considerable delay of at least five to six months for the first supplies of vaccine to become available after the isolation of the strain and availability of the candidate vaccine virus to vaccine manufacturers. By this time, the virus is likely to have already infected millions of people worldwide, causing significant mortality, morbidity and economic loss.Passive immunization through broadly neutralizing antibodies which bind to multiple, structurally diverse strains of influenza could be a promising solution to address the immediate health threat of an influenza pandemic while vaccines are being developed. These products may also have a role in seasonal influenza as an alternative to other options such as antivirals for the treatment of severe acute respiratory illness due to influenza.This article provides an overview of the current clinical pipeline of anti-influenza antibodies and discusses potential uses and the challenges to product development.

Monoclonal antibodies as anti-infective products: a promising future?

“…For example, within the context of ongoing product development targeting influenza, for which promising results were obtained in ferret models and early clinical development, broadly neutralizing mAbs might be suitable at the emergence of a pandemic outbreak, at least for specific at-risk groups such as exposed contacts and healthcare professionals [52e54]. In that scenario, they could be used to bridge the time gap before availability of strain-specific vaccines [55].…”

Meeting report: Global vaccine and immunization research forum, 2018

“…For influenza, broadly protective mAbs have applications in the treatment of severe influenza, prevention of infection when vaccination is not feasible (such as early during a pandemic), and for vaccine antigen discovery. The influenza mAb pipeline includes candidates with confirmed effects on virus shedding when administered post-challenge in CHIMs [24].…”

“…GVIRF participants noted that school-based programs could provide a platform for delivery of additional services to adolescents but must be complemented by programs targeting the 263 million children who are out of school. To facilitate high coverage, social mobilization is needed to increase awareness and reduce vaccine hesitancy [24,25].…”

The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis

“…In addition, passive immunotherapy utilising broadly neutralising mAbs has been proposed as a promising treatment and there has been extensive characterisation of these mAbs and their binding epitopes on HA. As described in several recent reviews [5][6][7][8], these are two main classes of broadly neutralising mAbs known to bind to highly conserved domains in the head and stalk of HA respectively.…”