Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine

Neuraminidase (NA) is an influenza surface protein that helps to free viruses from mucin-associated decoy receptors and to facilitate budding from infected cells. Experiments have demonstrated that anti-NA antibodies protect animals against lethal influenza challenge by numerous strains, while decreasing pulmonary viral titers, symptoms, and lung lesions. Studies in humans during the influenza A/H3N2 pandemic and in healthy volunteers challenged with influenza A/H1N1 showed that anti-NA immunity reduced symptoms, nasopharyngeal viral shedding, and infection rates. Despite the benefits of anti-NA immunity, current vaccines focus on immunity against hemagglutinin and are not standardized to NA content leading to limited and variable NA immunogenicity. Purified NA has been shown to be safe and immunogenic in humans. Supplementing current vaccines with NA may be a simple strategy to improve suboptimal effectiveness. Immunity against NA is likely to be an important component of future universal influenza vaccines.