Researchers from the University of Chicago, Scripps Research Institute, and Icahn School of Medicine at Mount Sinai report a new class of broadly neutralizing antibodies targeted against regions near the base of the influenza surface glycoprotein hemagglutinin (HA), which the authors named anchor antibodies in Nature Scientific Journal. The HA proteins on the surface of influenza virions are broken into two major domains, the HA-head and the HA-stalk. Antibodies that target the HA-head domain are critical components of immune protection against influenza infections, but the lack of conservation within these domains limits their protective capabilities to a narrow selection of influenza viruses. However, vaccines that target highly conserved portions of HA may provide immunity against a more diverse array of influenza viruses. The previously uncharacterized antibody class the authors identify provides a novel target for universal influenza vaccine design.
The Centers for Disease Control and Prevention (CDC) estimate that between 9 million and 41 million influenza infections occur annually resulting in 12,000 to 52,000 deaths. Influenza vaccinations are a powerful disease prevention tool, but the high mutation rates and numerous influenza subtypes pose significant challenges. A universal vaccine that targets highly conserved regions of the virus, is effective against a wide range of influenza subtypes, and induces effective immunological memory would lessen the need to administer and update influenza vaccines annually.
The authors generated 358 antibodies from the blood of individuals who were either infected with seasonal influenza, vaccinated against seasonal influenza, or part of a phase 1 universal vaccine clinical trial. The researchers found that nearly half of the antibodies tested targeted the conserved HA-stalk, and the majority (~80%) of those antibodies were directed to uncharacterized regions of the HA-stalk. The antibodies that are directed toward the uncharacterized stalk regions are referred to as “anchor-binding” antibodies, and were found to bind both a broad assortment of human H1N1 viruses and an H1N2 swine influenza virus. Additionally, a subset of the antibodies demonstrated neutralization activity toward an H2N2 virus, which suggests anchor-binding antibodies can also target non-H1 influenza viruses. Importantly, the antibodies were represented across many of the volunteers’ samples, which suggests they are common components of the immune antibody repertoire. Furthermore, anchor-binding antibodies were shown to have the ability to neutralize viruses carrying known immune evasion mutations, limiting the ability of viruses to develop into escape variants. The findings from the Guthmiller et al. (2022) study provides exciting insight on a previously undescribed class of antibodies and offers the next steps to developing universal influenza vaccines.
Guthmiller, J.J. et al. (2022) Broadly neutralizing antibodies target a hemagglutinin anchor epitope. Nature. 602: 314-320.