Literature Commentary by Dr. John G. Bartlett: Avian Influenza, July 2007
Sandbulte MR, Jimenez GS, Boon AC, Smith LR, Treanor JJ, Webby RJ. Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans. PLoS Medicine. 2007;4:e59 The authors hypothesized that the neuraminidase of the H5N1 and the endemic human H1N1 viruses might show antigenic cross-protection against H5N1 influenza virus.
Methods: Mice were immunized with gene segments of H5N1 (A/Vietnam/1203/04), H1N1 (A/New Caledonia/20/99), and H1N1 (A/Puerto Rico/34, PR8) which were used for gene segments for cloning into plasmids for virus rescue and gene reassortment by reverse genetics. The reassortant viruses include the neuraminidase gene (NA) from the human A/New Caledonia/20/99, designated "PR8-huN1," and the avian NA gene segment A/Vietnam/1203/04, designated "PR8-avN1." A DNA vaccine was developed by cloning the NA sequence from huN1. Mice were vaccinated with this vaccine and they were then challenged with 10- and 100-fold the doses lethal to 50% of mice (MLD50).
Results: Results showed protection against mortality which was complete with PR8-huN1 and was partial with PR8-avN1 and A/Vietnam/1203/04. These data are shown in the Table, which compares the survival in mice given the N1 vaccine vs saline controls.
In addition, sera in vaccinated mice was given intraperitoneally to naive mice prior to challenge with 10 MLD50 of A/Vietnam/1203/04. This resulted in complete protection against mortality. Serum from huN1-vaccinated mice was partially protective with survival of 6/13 (46%).
Conclusions: The authors concluded that humoral immunity elicited by huN1 is partially protective against H5N1.
Comment: This is a potentially important paper because it suggests that vaccination against seasonal influenza which contains N1 antigen (which it does) may confer partial protection against H5N1. One problem is that the current seasonal influenza vaccines have the hemagglutinin (HA) as the principal target, so the NA is not standardized and the amount of antibody varies from batch to batch. Nevertheless, the implication here is that the use of seasonal influenza vaccine may provide some protection against pandemic H5N1.