Induction of cross-neutralizing antibody against H5N1 virus after vaccination with seasonal influenza vaccine in COPD patients

Archival serum samples from elderly individuals with underlying chronic obstructive pulmonary disease (COPD) who were enrolled in a double-blind case-control study of seasonal influenza vaccine efficacy were assayed for cross-neutralizing antibody formation to avian influenza A (H5N1) virus. Of 118 serum samples, 58 were collected from influenza vaccinees (mean age 68.5y), and 60 from placebo controls (mean age 68.4y) who received vitamin B injections. Blood samples were collected before and at 1mo after seasonal influenza vaccination from all subjects; in addition, for a longitudinal follow-up period of 1y paired-blood samples were collected again from subjects who developed acute respiratory illness. Hemagglutination inhibition assay for antibodies to influenza A (H1N1), influenza A (H3N2), and influenza B viruses was carried out to determine the serological response to vaccination, and to diagnose influenza viral infection, while microneutralization assays were performed to detect cross-reactive antibody to H5N1 virus. Pre-existing cross-reactive H5N1 antibody at reciprocal titer 10 was found in 6 (10.3%) vaccinees and 4 (6.7%) placebo controls. There was no change in H5N1 antibody titer in these subjects after vaccination. On the other hand, 3 (5.2%) vaccinees developed seroconversion to H5N1 virus at 1mo after vaccination, even though they had no pre-existing H5N1 antibody in their first blood samples. No cross-neutralizing antibody to H5N1 virus was detected in the placebo controls or in the 22 influenza patients, suggesting that influenza vaccination, but not influenza virus infection, induces cross-neutralizing antibody against avian influenza H5N1 virus.