Researchers Test Novel Nanoparticle Flu Treatment

While vaccination remains the leading line of defense to prevent influenza infections, developing better antiviral drugs promises to be another tool that can be used in the fight against the flu. Using nanotechnology to trick the influenza A virus, a team of researchers is working on a new treatment option for people suffering from the viral infection.

With the flu season around the corner, the Centers for Disease Control and Prevention (CDC) emphasize the importance of receiving the influenza vaccine, the annual shot that health experts say is the best form of protection against the flu. Each year, the vaccine’s formulation is set based on surveillance data on circulating influenza A and B viruses. Gradual antigenic drifts cause changes in the two surface proteins of an influenza virus, hemagglutinin (H) and the neuraminidase (N), and the flu vaccine is adjusted year to year to best inoculate against the viruses currently circulating in the population. It is when an influenza virus goes through a sudden antigenic shift, defying months of collected surveillance data, that a seasonal flu shot may fail to prevent illness and a larger flu outbreak.

A team of researchers in the United States and South Korea recently conducted a study on a novel flu treatment to circumvent this annual uncertainty concerning influenza. Their paper, published in the journal Nature Nanotechnology, focuses on an alternative to vaccines and the antiviral neuraminidase inhibitor treatments which target the viral neuraminidases of the influenza virus in people who are sick with the flu. The virus attacks by using hemagglutinin to attach to sialic acid on the surface of lung cells, while neuraminidase allows the virus to release in order to spread and infect cells. In their study, the researchers created a nanoparticle coated in sialic acid that when misted into the lungs essentially acts as a decoy to attract and trap influenza virus molecules. They tested their formula on mice infected with H1N1 influenza and found that the nanoparticle treatment blocked the virus from attaching to and entering lung cells, protecting 75% of mice from influenza-caused death.

Study author Robert J. Lindhardt, PhD, of the Department of Chemistry and Chemical Biology at Rensselaer Polytechnic Institute, recently answered some of Contagion's questions about the study and its implications for a novel flu treatment:

How does the treatment approach in your study avoid the effects of antigenic influenza changes, keeping it effective year after year?

"There are two types of influenza viral antigens, hemagglutinin (H) and neuraminidase (N). The hemagglutinin (H) antigen binds to sialic acid on the surface of lung cells. Our approach captures the influenza virus with a nanoparticle containing multiple copies of sialic acid. While it is possible that the H antigen could change through mutation, if it changes so much that it cannot be captured by sialic acid-containing nanoparticles it is also unlikely that the virus would still be able to bind to the sialic acid on the surface of lung cells and cause an infection. It is for this reason that we believe resistance will not be as great a problem as it has been with neuraminidase inhibitors, the standard drugs used to treat influenza."

We are still learning a lot about nanoparticles, how they impact our bodies and our environment, and how safe they are. How does the nanoparticle in your research offer both effectiveness and safety?

"This is a valid question and the safety and toxicity of our nanoparticle based agent has not been thoroughly tested. If we encounter a safety problem, in principle, we could change the chemical composition of our nanoparticle. The important aspect of this study is not the chemical composition of our underlying nanoparticle but rather its size, geometry, and the optimized spacing of the sialic acid groups on its surface and this could be accomplished using many different types of nanoparticles."

Do you see a treatment option such as this one as working in conjunction with annual vaccines? Do you think that if we have a highly effective treatment available, people we move away from getting annual vaccines, with all their imperfections?

"Effective vaccines are and will probably remain the best choice as they are generally inexpensive and prevent infection in the first place. In many cases, however, vaccines are ineffective. Also once you contract an infectious disease it is usually too late to vaccinate for protection. Finally, there are many people for whom vaccines cannot be used, like the immunocompromised, and in such cases antiviral therapeutics are the only choice. If one can tolerate annual vaccination it is typically recommended. If the disease is acquired by a non-vaccinated person or if the annual vaccination fails to protect then a therapeutic such as a neuraminidase inhibitor is required. One day a hemagglutinin binding agent, like our sialic acid-containing nanoparticles, might be used either alone or in concert with a neuraminidase inhibitor to effectively treat influenza."