Evaluation of Cross-Reactivity of Influenza Vaccine

To examine cross-reactivity we have examined pre-vaccination and post-vaccination serum samples that were acquired from 18 donors that received the 2007/2008 TIV that had been reformulated with the Solomon Islands (H1N1) virus after containing the New Caledonia (H1N1) strain for 6 years prior. Interestingly, a comparison of the sera samples for Cartesian axes of avidity (Y axis) and Solomon Islands/New Caledonia cross-reactivity (X-axis) suggested that vaccination with the new H1N1 strain (Solomon Islands) actually triggered a parallel loss in both the avidity and cross-reactivity of the H1-specific antibodies in strong responders. This analysis could provide at least one clue as to why the 2007-2008 seasonal influenza vaccine exhibited lackluster performance: the poor quality (avidity/potential for cross-reactivity) of the influenza-specific antibody generated against the Solomon Islands vaccine strain in immunized individuals likely could not protect against variant viruses with even minor sequence changes in the dominant antigens. Collectively, the ability to assess both T cell and B cell cross-reactivities against influenza can be pivotal in evaluating whether prior seasonal influenza vaccine inoculation(s) have the potential of limiting virus replication and disease caused by other newly emergent pandemic influenza isolates.

Vaccination with the 2007/2008 TIV triggers a loss of influenza-specific antibody avidity and cross-reactivity. Antibody forensics was used to evaluate the reactivity/avidity of serum antibodies specific for the Solomon Islands and New Caledonia strains of virus; the ratio of the signals was used as a cross-reactivity index. Pre-vaccinated donor sera (left graph) was more avid for influenza virus and showed a higher level of cross-reactivity between the New Caledonia and Solomon Islands strains than post-vaccination sera samples (right graph) from the same donors. Each data point represents a distinct donor; circled is a group of low-cross-reactivity, low-avidity responses obtained from high-responding donors after vaccination.