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Insight into a class of mAbs that offers broad protection against the flu

Protein engineering, synthetic biology, LOCKR, bacterial expression, cell signalingAs we enter into the 2019 flu season, many people are also gearing up to protect themselves from this contagious, potentially life-threatening illness by getting their annual flu shot. The high mutation frequency of the flu virus helps it evolve to escape recognition and destruction by our immune system, making it problematic to eradicate.

In order to be effective against mutated variants of influenza viral proteins, antibodies generated by our immune system should ideally be both broadly protective and cross-reactive. A recent article published in Nature Communications by Adachi et al. shed light on such a class of cross-reactive antibodies. These antibodies were generated by B cells in lung germinal centers (GC) in response to influenza viral replication. The research group identified a population of 163 individual lung GC B cell clones that secreted cross-reactive antibodies. They then analyzed the binding frequencies of each clone to hemagglutinin (HA), a glycoprotein that plays a critical role in viral attachment to and fusion with target cells. From these results, they mapped the dominant epitope of these antibodies to the long alpha helix (LAH) portion of the HA2 region of HA, where 61% of the secreted IgGs bound. The research group observed that while these LAH mAbs were non-virus-neutralizing, that they were broadly protective, and when tested in mice, could even offer protection against lethal infection of certain influenza virus strains. The research group then went on to establish that it was the post-fusion HA antigen that was able to induce these cross-protective LAH mAbs.

This study demonstrates how important it is to understand the way our immune system responds to the influenza virus and greatly serves to help us better understand this illness and, ultimately, to develop more effective vaccines and therapies to fight against this sickness.

Adachi Y, Tonouchi K, Nithichanon A, et al. Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies. Nat. Commun.. 10(1), 3883 (2019).

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