Influenza's Other Surface Protein

All of the licensed influenza vaccines and most of the candidates in clinical or pre-clinical development target the hemagluttinen (HA) antigen on the surface of the virus. This is partly because induction of antibodies against HA is a correlate of immune-mediated protection against influenza, making the surface protein a logical target for the production and quality assessment of vaccines.

Much less is known about the role of neuraminidase(NA), another influenza surface protein, in influenza immunity. There are no identified correlates of protection from disease for NA immunity and although regulatory authorities request that NA be included in seasonal influenza vaccines, their focus and attention has always been on the quantity and quality of HA. But data presented Wednesday by research fellow Judy Easterbrook at the Influenza Congress 2010 in Arlington, Virginia, suggest the inclusion of NA antigens in vaccine candidates might reduce the severity of influenza-related disease and increase cross-protection against the highly variable virus.

Easterbrook , a research fellow in the laboratory of Jeffery Taubenberger, chief of the viral pathogenesis and evolution section of the US National Institute of Allergy and Infectious Diseases, has made the study of NA a major focus of her work. (Taubenberger’s laboratory is best known, perhaps, for sequencing the viral genome of the mother of all flu strains, the H1N1 avian strain, or Spanish flu, that killed an estaimted 50 million people between 1918 and 1920.)

Easterbrook  vaccinated mice intranasally with virus-like particles expressing just the NA protein and then challenged the mice six weeks later with either the 2009 H1N1 pandemic strain or a more pathogenic H5N1 strain, comparing the results to controls. The unvaccinated mice died, while mice from the H5N1 or the H1N1 groups survived, had fewer lung titers, and shed less weight.

Easterbrook says blocking NA could reduce transmission and viral shedding by reducing lung titers and severity of disease. In fact, some hypothesize that NA immunity could explain why the 1968 pandemic caused by an H3N2 strain that originated in Hong Kong, while claiming one million lives, was not more severe as initially predicted. The Hong Kong strain shared internal genes and NA with the 1957 H2N2 Asian flu, and epidemiologists have speculated that pre-existing antibodies to NA or other internal proteins from the earlier pandemic may have resulted in far less disease and fewer casualties during the 1968 pandemic.