Influenza neuraminidase as a vaccine antigen

The neuraminidase protein of influenza viruses is a surface glycoprotein that shows enzymatic activity to remove sialic acid, the viral receptor, from both viral and host proteins. The removal of sialic acid from viral proteins plays a key role in the release of the virus from the cell by preventing the aggregation of the virus by the hemagglutinin protein binding to other viral proteins. Antibodies to the neuraminidase protein can be protective alone in animal challenge studies, but the neuraminidase antibodies appear to provide protection in a different manner than antibodies to the hemagglutinin protein. Neutralizing antibodies to the hemagglutinin protein can directly block virus entry, but protective antibodies to the neuraminidase protein are thought to primarily aggregate virus on the cell surface, effectively reducing the amount of virus released from infected cells. The neuraminidase protein can be divided into nine distinct antigenic subtypes, where there is little cross-protection of antibodies between subtypes. All nine subtypes of neuraminidase protein are commonly found in avian influenza viruses, but only selected subtypes are routinely found in mammalian influenza viruses; for example, only the N1 and N2 subtypes are commonly found in both humans and swine. Even within a subtype, the neuraminidase protein can have a high level of antigenic drift, and vaccination has to specifically be targeted to the circulating strain to give optimal protection. The levels of neuraminidase antibody also appear to be critical for protection, and there is concern that human influenza vaccines do not include enough neuraminidase protein to induce a strong protective antibody response. The neuraminidase protein has also become an important target for antiviral drugs that target sialic acid binding which blocks neuraminidase enzyme activity. Two different antiviral drugs are available and are widely used for the treatment of seasonal influenza in humans, but antiviral resistance appears to be a growing concern for this class of antivirals.