The WHO meeting on the role of neuraminidase in inducing protective immunity against influenza infection, 14 September 2008, Vilamoura, Portugal
Summary and meeting documents
During the last three years several reports were published indicating that influenza virus neuraminidase (NA) participates in inducing protective immunity against influenza infection. This information reinforced the discussion on neuraminidase as component of effective influenza vaccines. On 14 September 2008, The World Health Organization convened a meeting on the role on neuraminidase in inducing protective immunity against influenza infection with participation of the researchers from academia, representatives of National Regulatory Authorities and manufacturers. The meeting was held in conjunction with the 3rt European Conference on Influenza in Vilamoura, Portugal. The meeting's objectives were to review the current status of research in the area of immune responses elicited by influenza virus neuraminidase and discuss new approaches in the development of simpler and reproducible assays for detecting anti-NA immunity and quantify NA in commercial vaccines.
Results were presented showing that an immune response to human NA subtype 1 partially protects mice from a lethal low dose challenge with H5N1 influenza virus, and cross-protection against different H5N1 strains appears largely antibody-mediated. Cross-reactivity against NA of H5N1 viruses was also demonstrated in some human sera. Based on this data, it was suggested that immunization with seasonal influenza vaccines could induce some degree of resistance to H5N1 infection in humans. However, the results of another study indicate that specific antibodies against neuraminidase (H1N1) afforded very limited cross-protective immunity against H5N1 virus in an animal model.
Anti-NA immune responses induced by influenza vaccinations were discussed. It was noted by participants that additional research using carefully matched controls will strengthen current existing data, and that more results are needed from clinical studies that incorporate measurement of anti-NA responses to licensed or candidate vaccines. Efficacy studies to identify correlates of immunity will be necessary once assays are identified and standardized.
Assays to measure immune response to neuraminidase were reviewed. Information was presented on the development of a mini-neuraminidase inhibition (NAI) test which can be used to determine NAI titers in human sera or to assess the specificity and sensitivity of alternate NAI assays. It was broadly accepted that traditional neuraminidase inhibition assays are technically complex and have significant variability. There is not a standardized protocol and various labs are using various modifications. Studies to improve traditional assays and develop new tests to evaluate immune responses to NA are being elaborated. Standard protocols should be developed and collaboration for evaluation and standardization of assays is encouraged.
Finally, currently licensed influenza vaccines are inconsistent in the amount of neuraminidase included. Assays are needed to reliably measure and standardize the quantity of NA present in each vaccine. New assays are being developed and information on quantification of neuraminidase in vaccines by mass-spectrometry was presented. NA in vaccine formulations can be labile making stabilization of NA and NA activity a challenge. Additional process development and formulation research is needed to improve the stability of NA in vaccines.