Newly identified antibodies target a hard-to-spot region of the influenza virus

NewsGuard 100/100 Score

Researchers at the National Institutes of Health have identified antibodies targeting a hard-to-spot region of the influenza virus, shedding light on the relatively unexplored "dark side" of the neuraminidase (NA) protein head. The antibodies target a region of the NA protein that is common among many influenza viruses, including H3N2 subtype viruses, and could be a new target for countermeasures. The research, led by scientists at the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, part of NIH, was published today in Immunity.

Influenza, or flu, sickens millions of people across the globe each year and can lead to severe illness and death. While vaccination against influenza reduces the burden of the disease, updated vaccines are needed each season to provide protection against the many strains and subtypes of the rapidly evolving virus. Vaccines that provide protection against a broad range of influenza viruses could prevent outbreaks of new and reemerging flu viruses without the need for yearly vaccine reformulation or vaccinations. 

One way to improve influenza vaccines and other countermeasures is to identify new targets on the virus's surface proteins in "conserved" regions-;portions that tend to be relatively unchanged between different strains of the virus. Influenza NA is a surface protein containing a globular head portion and a narrow stalk portion. The underside of the NA head contains a highly conserved region with targets for antibodies-;known as epitopes-;that make it vulnerable to antibody binding and inhibition of the virus, as well as not being impacted by mutations common in drug-resistant strains. This region is termed the "dark side" due to its partially hidden location and relatively unexplored characteristics.

The researchers isolated human antibodies that target the NA dark side from the blood of two people who had recovered from influenza type A subtype H3N2, a major subtype of seasonal flu viruses. In lab tests, the antibodies inhibited propagation of viruses from subtype H2N2, the subtype that caused pandemic influenza in 1957-58, and H3N2 viruses from humans, swine, and birds. The antibodies also protected mice from lethal infection by a subtype H3N2 virus when given to the animals either one day before or two days after infection, showing that the antibody may treat and prevent influenza in this model. 

The scientists analyzed the structure of two of the antibodies while bound to NA using advanced microscopy techniques known as cryogenic electron microscopy. Each antibody targeted different, nonoverlapping regions of the dark side, demonstrating that this region has multiple areas that may be useful to explore for countermeasure development. 

These findings show that the NA dark side has unique, previously untapped epitopes that could be applied to the development of new vaccine and therapeutic strategies. They suggest that antibodies targeting the NA dark side could be useful in combination with antivirals or other types of antibodies for interventions against influenza, as they are effective against influenza viruses with drug-resistant mutations. The researchers also note that NA dark side targets could be included in the next generation of broadly protective vaccines against influenza.

Source:
Journal reference:

Lederhofer, J., et al. (2024) Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase. Immunity. doi.org/10.1016/j.immuni.2024.02.003.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Study reveals waning antibody response to monkeypox vaccine over time