Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine

Abstract

Thirty adults were tested for humoral and cellular immune responses following immunization with the trivalent inactivated influenza vaccine. Modest but significant inverse correlations between the baseline and the fold changes in the number of IFNgamma-producing cells and the levels of neutralizing antibodies were observed. Specific increases in proliferative responses in the CD8 CD45RA+ population were noted after vaccination. Minimal correlations between neutralizing antibody titers and the number of IFNgamma-producing cells in terms of prevaccination levels or fold increases were observed. These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the trivalent inactivated influenza vaccine.

Figure 1

Relationship between the number of IFNγ producing cells at baseline and peak fold increase after immunization using ELISPOT assay. Linear regression analysis was performed using all data available for the three time points for the H3N2 A/Wisconsin/67/05 strain (left panel) and the H1N1 A/New Caledonia virus/20/99 (right panel). SFU= spot forming units

Figure 2

Increase in CD8 CD45RA+ cells capable of virus specific proliferation after influenza vaccination. Typical flow cytometry plot using carboxyfluorescein succinimidyl ester (CFSE) based assay for an individual donor at prevaccination and at Day 64 post vaccination. Media and Phytohemagluttinin controls are shown. CFSE labeled PBMC were stimulated with A/New Caledonia virus/20/99 for 6 days and then surface stained for CD3,CD8 and CD45RA.Cells were analyzed on Flow Jo software by gating on live lymph cells, then CD3 vs side scatter, then CD8 vs. side scatter and then CD45RA vs CFSE. Bolded numbers in the quadrants refers to the percentage of CD8/CFSE+/CD45RA+ or CD8/CFSE+/CD45RA− cells.

Figure 3

Relationships between frequencies of IFNγ producing cells and the neutralizing antibody titers. All analyses were performed using linear regression analysis. A- Correlations between the prevaccination numbers of IFNγ producing cells and prevaccination neutralizing antibody titers for H3N2 A/Wisconsin/67/05 prevaccination ( left, r² = 0.003 p= 0.74 )and H1N1 A/New Caledonia virus/20/99 (right, r² = 0.25 p=0.0049). SFU = spot forming units. B- Correlations between the peak post-vaccination fold increases in the number of IFNγ producing cells and peak post-vaccination fold increases in neutralizing antibody titers for H3N2 A/Wisconsin/67/05 (left, r² = 0.102 p= 0.083) and H1N1 A/New Caledonia virus/20/99 ( right, r² = 0.001 p= 0.85). SFU = spot forming units. C– Correlations between prevaccination neutralizing antibody titers and peak fold increase in IFNγ producing cells for H3N2 A/Wisconsin/67/05 (left, r² = 0.005 p= 0.70) and H1N1 A/New Caledonia virus/20/99 (right, r² = 0.00005 p= 0.97). SFU = spot forming units. D- Correlations between prevaccination IFNγ producing cells and peak fold increase in neutralizing antibody titers for H3N2 A/Wisconsin/67/05 (left, r² = 0.058 p= 0.196)and H1N1 A/New Caledonia virus/20/99 (right, r² = 0 .132 p= 0.048). SFU = spot forming units