Investigating original antigenic sin responses to H5N1 influenza viruses

H5N1 influenza A virus remains a global threat since its outbreak in 1997. Its re-emergence in 2003 spread from Asia to Europe, the Middle-East and Africa, raising concerns of a possible pandemic. While stockpiling of H5N1 prepandemic vaccines has been initiated, strain prediction is difficult due to the emergence of distinct clades/subclades. Antigenic variation between vaccine and pandemic strains may confer cross-protection or result in antigenic sin, in which the immune response is directed against the original strain rather than the novel protective antigenic determinants. Observed between strains that have undergone antigenic drift, this misdirected response may compromise protective immunity. This study was carried out to determine the extent to which antigenic sin interferes with immune responses to the potentially pandemic influenza H5 subtype. We immunized mice with a DNA vaccine encoding the full length HA from influenza A/Vietnam/1194 followed by a vaccine encoding HA of drifted H5N1 strains, ranging in genetic identity from 100%- 88%. We are currently assessing responses directed against either the primary or the drifted strain by microneutralization using a pseudotyped lentivirus bearing HA from the respective H5N1 strains. By examining antigenic sin due to H5N1 viruses, we can better understand the behavior of the virus as it circulates in the human population, and therefore improve preparedness in the context of H5N1 vaccine development and pandemic planning.