B-cell receptor and antibody repertoire recognizing influenza hemagglutinin and neuraminidase (HA/NA-specific BCR repertoire)

The B-cell receptor (BCR) and antibody repertoire recognizing influenza hemagglutinin (HA) and neuraminidase (NA) is the primary component of the adaptive humoral immune response against influenza viruses (Nature, 2016, doi:10.1038/nature18414). Hemagglutinin facilitates viral entry by binding to host cell sialic acids, while neuraminidase enables the release of progeny virions from the host cell surface (Science, 2019, doi:10.1126/science.aau4515). Antibodies within this repertoire neutralize the virus by blocking these critical steps in the viral life cycle. This repertoire is highly diverse and is shaped by a lifetime of viral exposures and vaccinations through processes like V(D)J recombination and somatic hypermutation (Cell, 2019, doi:10.1016/j.cell.2019.03.035). Therapeutic interventions, such as seasonal and universal influenza vaccines, aim to expand and refine this repertoire to provide broad protection against drifting viral strains. Monoclonal antibodies isolated from these repertoires, such as MedI8852 and VIS410, are being investigated as passive immunotherapies for severe influenza cases. A major challenge in targeting this repertoire is "original antigenic sin," where the immune system preferentially responds to antigens from the first influenza strain encountered in childhood (NIH, NIAID, 2023). Understanding the landscape of this repertoire is essential for developing next-generation vaccines that can elicit more durable and cross-reactive immunity.

Other names

Anti-influenza antibody repertoireHA-specific B-cell repertoireNA-specific B-cell repertoireInfluenza-specific humoral immune repertoireAnti-HA/NA antibodies

Vaccines act as immunogens to stimulate the expansion and somatic hypermutation of B-cells within this repertoire, leading to the production of high-affinity antibodies. These antibodies provide protection by binding to the hemagglutinin head to block viral attachment, the hemagglutinin stalk to block membrane fusion, or the neuraminidase active site to prevent the release of viral progeny from infected cells (PubMed, PMID: 30765615).