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Title: Influenza neuraminidase as a vaccine antigen

item Sylte, Matthew
item Suarez, David

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 2/25/2009
Publication Date: 6/1/2009
Citation: Sylte, M.J., Suarez, D.L. 2009. Influenza neuraminidase as a vaccine antigen. In: Compans, R.W., Orenstein, W.A., editors. Vaccines for Pandemic Influenza. New York, NY: Springer. p. 227-242.

Interpretive Summary: Influenza virus causes infection and disease in a number of avian and mammalian species. The use of vaccination can be used to prevent or reduce clinical disease with the virus, and antibody protection from these vaccines is key. Antibodies to two different influenza virus proteins, the hemagglutinin and the neuraminidase proteins, are the keys for protection. The neuraminidase protein is highly diverse, and 9 different antigenic subtypes of the protein are found in nature. Antibody to one subtype only protects against viruses of the same subtype, and not to other subtypes. For vaccination to be optimally effective, you must vaccinate with the correct neuraminidase subtype. The neuraminidase protein is also the target of two commonly used anti-viral drugs. Although these drugs can be effective at reducing disease symptoms in humans, some drug resistance has emerged that limits treatment effectiveness in some people.

Technical Abstract: The neuraminidase protein of influenza viruses is a surface glycoprotein that has 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 how the neuraminidase antibodies provide protection appears to be different than from antibodies to the hemagglutinin protein act. 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 9 distinct antigenic subtypes, where there is little cross protection of antibodies between subtypes. All 9 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. The neuraminidase protein even within a subtype can have a high level of antigenic drift, and vaccination has to specifically be targeted to the circulating strain to have optimal protection. The levels of neuraminidase antibody also appear to be critical for protection, and there is concern that human influenza vaccines don’t 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 treatment of seasonal influenza in humans, but anti-viral resistance appears to be a growing concern for this class of antivirals.