Monoclonal Antibodies Target Hard-to-Spot Region of the Influenza Virus, Shed Light on Unexplored “Dark Side” of Flu

Experts have recently discovered a promising development in the fight against influenza by discovering new antibodies targeting the 'dark side' of the virus protein.

(Photo: Unsplash/ National Cancer Institute)

Dark Side of Influenza Virus

Influenza is a highly contagious viral infection that can cause severe illness and life-threatening complications. This disease is common in all parts of the world and can be easily spread through coughing or sneezing.

According to the World Health Organization (WHO), there are around one billion cases of seasonal influenza every year, including 3-5 million cases of severe illness. It is also attributed to 290,000 - 650,000 annual deaths.

Vaccination remains one of the best ways of reducing the burden of influenza and has been used for more than 60 years. Although vaccines may be less effective in older people, they can make the disease less severe and reduce the chance of complications and death. Previous studies reveal that the flu vaccine can lower the risk of flu by 40-60% as long as the vaccine matches the spreading of flu viruses.

However, vaccines need to be updated each season to protect against the strains and subtypes of the rapidly evolving influenza virus. Vaccines that offer protection against a broad range of flu viruses can prevent outbreaks of new and reemerging strains without annual vaccine reformulation or vaccinations.

To improve influenza vaccines and other countermeasures, experts recognize the need to identify new targets on the virus's surface proteins. These proteins are found in conserved regions that seem to remain unchanged between various influenza virus strains. Also known as influenza neuraminidase (NA), this surface protein is a virulence factor that modifies the host's response to infection.

Influenza NA has a globular head portion and a narrow stalk portion. It contains a highly conserved region with targets for antibodies called epitopes. This region makes it vulnerable to antibody binding and inhibition of the virus. It is also not affected by mutations that commonly happen to drug-resistant strains. This region is called the "dark side" because of its partially hidden location and unexplored characteristics.

Targeting Conserved Sites of Vulnerability

At the National Institutes of Health, researchers have identified antibodies that can target a hard-to-spot region of the influenza virus. The result of their study is discussed in the paper "Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase."

Led by Julia Lederhofer, the research team isolated human antibodies that target the NA dark side from the blood samples of two people who had recovered from influenza type subtype H3N2, a major subtype of seasonal influenza viruses.

In laboratory tests, the antibodies hindered the propagation of viruses from subtype H2N2, the subtype that brought pandemic influenza in 1957-1958. It also inhibited H3N2 viruses from humans, birds, and swine. Upon testing their effectiveness, the antibodies were seen to protect mice from lethal infection by a subtype H3N2 when given either one day before or two days after getting infected. This indicates that the antibody can be used in treating and preventing influenza.

The experts also analyzed the structure of two antibodies while being bound to NA using advanced microscopy techniques called cryogenic electron microscopy. Each antibody targeted various nonoverlapping regions of the dark side, showing that this region has multiple areas that can be useful for developing countermeasures.

This study reveals that the NA dark side has unique, previously untapped epitopes that can be applied to developing new vaccines and therapeutic strategies. The research team also noted that NA dark side targets could be included in the next generation of broadly protective vaccines against influenza.