Antibodies that target flu’s ‘stalk’ protect people

Antibodies that target the “stalk” of the flu virus—the part that doesn’t change often—offer protection in humans, according to a new study.

Researchers say the discovery could bring the scientific community a step closer to developing a universal vaccine.

“Our research is the first to demonstrate that scientists are right in attempting to develop antibodies that target this specific location as a novel universal influenza virus vaccine candidate,” says Aubree Gordon, a professor of epidemiology at the University of Michigan School of Public Health. “This study addresses an important gap and provides information to support the further development of novel influenza virus vaccines.”

Heads and stems

The flu virus is covered with two types of proteins: hemagglutinin and neuraminidase, which give rise to their names (H1N1, for example). The current flu vaccine targets the head of the hemagglutinin, a lollipop-like structure, which is the part that changes most often. Every season, researchers develop flu vaccines that target this part of the virus.

Researchers believe that if they target the stem of the hemagglutinin, instead of the head, it would allow them to prevent a wider range of flu viruses.

Flu cases in Nicaragua

For the new study, which appears in Nature Medicine Research, scientists looked at naturally occurring influenza cases in a cohort investigators have followed in Nicaragua for years. After one member in a household was determined to have the flu, researchers took blood samples to test the rest of the household. They looked at who was infected with the virus antibodies and who got sick.

“Once someone in the house has been diagnosed, we go into the household very rapidly and then we followed them for two weeks to see who gets the flu,” Gordon says. “That way, we can get a blood sample and measure antibody levels pre-exposure and then see if they get infected (and if) they get sick.”

Traditionally, an antibody concentration of 1:40 (measured in the hemagglutination inhibition assay) has been used as a 50 percent correlate of protection from clinical disease—meaning that half of the people who have those levels will be protected from influenza.

In the study, researchers found a similar protection, corroborating the idea that the field study design is sound to examine correlates of protection. They also found that a rise of four times in the amount of stalk antibody levels correlated with 42 percent reduction in influenza infection.

Universal vaccines?

“We were able to show that stalk antibodies do correlate with protection,” Gordon says. “That is great news as it supports the idea that stalk antibodies may be able to provide protection against influenza and could enable scientists to design a broader, more effective influenza vaccine.”

“While there are caveats and further studies needed, this is good news for the development of stalk-based universal influenza virus vaccines,” Krammer says. “It seems we are on the right track.”

The study also showed new tests can be used in flu research.

“An additional finding of this study is that ELISA-based readouts can be used as independent correlate of protection,” Krammer says. “ELISAs are binding assays and do not indicate functionality, but are much easier and quicker than functional assays.”

Additional coauthors are from the University of Michigan, the Icahn School of Medicine, the St. Jude Center of Excellence for Influenza Research and Surveillance, and the Center for Research on Influenza Pathogenesis and Centers of Excellence for Influenza Research and Surveillance. Partners in Managua, Nicaragua, include Laboratorio Nacional de Virología and Centro Nacional de Diagnóstico y Referencia and Centro de Salud Sócrates Flores Vivas, both of the Ministry of Health and Sustainable Sciences Institute.

The National Institute for Allergy and Infectious Diseases NIAID Centers of Excellence in Research and Surveillance, the Department of Defense, PATH, the Bill and Melinda Gates Foundation, and GlaxoSmithKline funded the work.

Source: University of Michigan