Immunogenicity and cross-reactivity of 2009-2010 inactivated seasonal influenza vaccine in US adults and elderly

Abstract

The campaign of 2009-2010 Northern Hemisphere seasonal vaccination was concurrent with the 2009 H1N1 pandemic. Using a hemagglutination inhibition (HAI) assay, we evaluated the immunogenicity and cross-reactivity of 2009-2010 inactivated trivalent influenza vaccine (TIV) in US adult and elderly populations. Vaccination of TIV resulted in a robust boost on the antibody response of all subjects to seasonal A/Brisbane/59/2007 (H1N1) and A/Uruguay/716/2007 (H3N2) with over 70% of recipients reaching a seroprotective titer of 40. B/Brisbane/60/2008 was the least immunogenic among the three seasonal vaccine strains with <30% of TIV recipients reaching a seroprotective titer of 40. TIV vaccination also induced a moderate boost on the pandemic specific antibody responses. Twenty-four percent of adults and 36% of elderly reached a seroprotective HAI titer of 40 or more against pandemic A/South Carolina/18/2009 (H1N1) after receiving TIV compared to 4% and 7% at the beginning of vaccination, respectively. In addition, 22% of adults and 34% of elderly showed an increase of 4-fold or more in A/South Carolina/18/2009 specific HAI titers after TIV vaccination. The pandemic specific cross-reactive antibodies strongly correlated with the post-vaccination HAI titers against the seasonal H3N2 vaccine strain in all subjects.

Figure 1. Hemagglutination inhibition (HAI) titers against 2009–2010 seasonal vaccine strains.

Serum samples collected from US healthy volunteers vaccinated with 2009–2010 inactivated unadjuvanted trivalent influenza vaccine (TIV) were tested by HAI assay using 0.5% turkey erythrocytes. The geometric mean titers (GMTs), the seroprotection rates (the proportion of subjects having an HAI titer ≥40) before and 21 days after TIV administration, and the seroconversion rates (the proportion of subjects having a ≥4-fold increase in HAI titers) were plotted according to the age distribution of vaccinees for A/Brisbane/59/2007 (H1N1) (A and D), A/Uruguay/716/2007 (H3N2) (B and E), and B/Brisbane/60/2008 (C and F), respectively. The 95% CI for individual HAI GMTs are shown as error bars. The dotted lines indicate HAI titer of 40.

Figure 2. Hemagglutination inhibition (HAI) titers against 2009 pandemic H1N1 viruses.

Serum samples collected from US healthy volunteers vaccinated with 2009–2010 inactivated unadjuvanted trivalent influenza vaccine (TIV) were tested for cross-reactivity against 2009 pandemic H1N1 viruses by HAI assay using 0.5% turkey erythrocytes. The pandemic influenza specific seroprotection rates (the proportion of subjects having an HAI titer ≥40) before and 21 days after TIV administration and the seroconversion rates (the proportion of subjects having a ≥4-fold rise in HAI titers) were plotted according to the age distribution of vaccinees for A/California/07/2009 (H1N1) (A and F), A/Iraq/8529/2009 (H1N1) (B and G), A/Ontario/RV3226/2009 (H1N1) (C and H), A/South Carolina/18/2009 (H1N1) (D and I) and A/England/195/2009 (H1N1) (E and J), respectively. * indicates the corresponding seroconversion rate in panel F, G, H, I, and J.

Figure 3. Correlation of antibody titers specific for seasonal vaccine strains and pandemic viruses after seasonal vaccination.

Serum samples were collected on 21 days after administration of 2009–2010 inactivated unadjuvanted trivalent influenza vaccine (TIV) in US healthy adults and elderly. An HAI assay was performed using 0.5% turkey erythrocytes. A correlation analysis between seasonal strain specific HAI titers and pandemic strain specific HAI titers was performed using nonparametric Spearman's ρ test by JMP Version 7. The scatterplots of HAI titers are shown in the presence of 95% bivariate normal density ellipses (indicating the distribution of 95% of individual data points plotted) and corresponding p values. A, A/California/07/2009 (H1N1) vs A/Uruguay/716/2007 (H3N2); B, A/South Carolina/18/2009 (H1N1) vs A/Uruguay/716/2007 (H3N2).