Influenza: a promising universal llama-derived antibody therapy

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A global research team with scientists from Janssen (Beerse, Belgium), the Scripps Research Institute (CA, USA), the University of Hong Kong, the University of Pennsylvania (PA, USA) and more have reported their success in generating a novel alternative influenza therapy, using single-domain antibodies (sdAbs) isolated from llamas, in their article entitled, ‘Universal Protection against Influenza Infection by a Multi-domain antibody to Influenza Hemagglutinin,’ published in the journal, Science.

With the use of broadly neutralizing sdAbs, isolated from influenza-immunized llamas, the team was able to create a highly potent multi-domain antibody (MDAb) namely, MD3606. The multi-domains characterizing this antibody allow it to target numerous epitopes at once, rendering it near-universally protective. This is important for controlling the highly variable antigenic properties of viral strains circulating each flu season.

MD3606, carried by an adenovirus vector, was administered to immunodeficient mice, intranasally in preclinical trials; overcoming previous attempts and showing promise by providing long-lasting, sustained immunity against lethal doses of varied influenza types, both in human influenza A and B strains and avian-borne strains like H1N1.

With flu being a continued threat year upon year, most adversely affecting those who are immunocompromised and the elderly; this work is a vital contribution towards finding a preventative measure against influenza that can be single-dose, maintained immunity and active against multiple strains allowing universality.

“Worldwide, there are more than one billion cases of influenza each year, resulting in up to 650,000 deaths. It remains one of the most serious public health challenges we face today. We believe that further innovations for influenza are urgently needed to address the shortcomings of current preventive and therapeutic options,” commented lead author, Dr Joost A Kolkman (Janssen Infectious Diseases). “In support of this mission and through unique global collaborations, we are focused on exploring multiple approaches which may provide the potential to prevent or treat influenza infections.”

Their strategy gives the opportunity for this therapy to be utilized for prevention as a first response to an influenza pandemic and comes at a time where current vaccines are outdated and limited in their coverage and sustainability. If these preclinical findings translate into humans, the approach may be a powerful tool to fight flu in vulnerable populations.

“While this manuscript suggests that a multi-domain antibody approach may hold potential as a strategy for the prevention of influenza A and B, this research is preclinical and further study is required. Janssen remains committed to pursuing innovation in influenza in collaboration with global, regional, and local partners,” concluded Kolkman.

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Sources: Laursen NS, Zhu X, Hoffman RMB et al. Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin. Science. doi:10.1126/science.aaq0620 (2018); www.eurekalert.org/emb_releases/2018-11/aaft-lap102918.php

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