South SFV Today

Viruses are known for their rapid evolution, which is why flu vaccinations are required annually. Some strains can be more severe than others, as seen in past pandemics such as the 1918 flu that resulted in 50 million deaths. Influenza remains a significant global health threat.

Taia Wang, MD, PhD, an associate professor at Stanford Medicine's Institute for Immunity, Transplantation and Infection, led a study that discovered how the composition of antibodies influences flu severity. The study found that a specific sugar molecule on antibodies affects whether individuals experience mild or severe symptoms.

The research demonstrated that manipulating antibody composition could reduce severe flu symptoms in mice, regardless of the strain. This discovery could be useful during future outbreaks and may apply to other infectious diseases.

Published in Immunity on November 13, the study suggests older individuals might be more susceptible to severe flu due to lower levels of this sugar molecule on their antibodies. The research team included Saborni Chakraborty, PhD; Bowie Cheng, PhD; Desmond Edwards; and Joseph Gonzalez, PhD.

A receptor called CD209 was identified as crucial in moderating inflammation during flu infections. Adjusting antibody composition activated this receptor without stopping viral replication inside lung cells.

Wang explained that severe influenza cases often result from excessive inflammatory responses rather than the virus itself. The experimental technique reduced inflammation without targeting a specific flu strain.

Antibodies contain sugar chains made up of various sugars like sialic acid. High levels of sialic acid were linked to milder symptoms because they bind to anti-inflammatory receptors on immune cells called alveolar macrophages.

The study showed that high-sialic acid antibodies reduced lung inflammation and improved oxygen exchange in mice exposed to lethal doses of different influenza subtypes. The findings suggest potential applications beyond influenza to other infectious diseases and inflammatory conditions.

Age-related declines in sialic acid levels might explain higher chronic inflammation rates among older adults, contributing to various age-associated diseases.

Wang is a consultant for Nuvig Therapeutics Inc., which provided reagents for this study. Collaborators included researchers from several institutions including the University of California, San Diego; National Jewish Health; Washington University School of Medicine; and the National Institutes of Health (NIH). Funding came from NIH grants and the Howard Hughes Medical Institute.

This report was initially published by Stanford School of Medicine.