T cell responses of HIV-infected children after administration of inactivated or live attenuated influenza vaccines

Abstract

Live-attenuated influenza vaccine (LAIV) prevents significantly more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the T cell responses to LAIV or TIV in HIV-infected children. IFN-gamma-ELISPOT for the three vaccine-contained influenza strains, two mismatched strains, and phytohemagglutinin (PHA), was performed at 0, 4, and 24 weeks postimmunization in 175 HIV-infected children randomly assigned to LAIV or TIV. The contribution of CD8 T cells to the influenza-specific response (CD8-ELISPOT) was evaluated by CD8-cell depletion. CD8 T cells accounted for > or =87% of the total influenza-ELISPOT. At baseline, total influenza-ELISPOT and CD8-ELISPOT values were similar or higher in TIV compared with LAIV recipients. Four and 24 weeks after TIV, total influenza-ELISPOT and CD8-ELISPOT results were significantly lower than baseline results (p < or = 0.001). Responses to PHA also tended to decrease at 4 weeks after TIV (p = 0.06), but rebounded to baseline levels at 24 weeks. Four weeks after LAIV, total influenza-ELISPOT responses to vaccine-contained strains A H3N2 and B significantly decreased. Other ELISPOT values at 4 weeks and all values at 24 weeks were similar to the baseline values. At 4 and 24 weeks, TIV compared to LAIV administration resulted in a significantly greater decrease in influenza-specific ELISPOT values for vaccine-contained influenza A strains (p < or = 0.02). Responses to PHA also tended to decrease more in TIV recipients (p = 0.07). HIV-infected children immunized with TIV had significant and persistent decreases in ELISPOT responses to influenza. LAIV administration suppressed ELISPOT responses less. The clinical significance of these findings deserves further study.

FIG. 1.

ELISPOT responses of TIV recipients. Data were derived from 85 HIV-infected recipients whose PBMCs were tested by ELISPOT after stimulation with PHA, influenza strains contained in the seasonal vaccine (A H3N2 Wyoming, A H1N1 New Caledonia and B Jilin), and mismatched influenza strains (A H3N2 Sydney and B Yamanashi). Bars represent medians for each group. Asterisks (*) indicate significant differences from baseline and the unequal sign (≠) indicates significant difference from week 4. (A) Total ELISPOT responses representing all PBMCs; (B) CD8 ELISPOT responses representing CD8 cells only. There were significant decreases in total and CD8 ELISPOT responses against all influenza strains at 4 and 24 weeks after vaccination (p ≤ 0.03). There was a trend toward a decrease in PHA-stimulated ELISPOT at 4 weeks after vaccination (p = 0.06) followed by a significant rebound at 24 weeks (p = 0.01).

FIG. 2.

ELISPOT responses of LAIV recipients. Data were derived from 90 HIV-infected recipients whose PBMCs were tested by ELISPOT after stimulation with PHA, influenza strains contained in the seasonal vaccine (A H3N2 Wyoming, A H1N1 New Caledonia and B Jilin), and mismatched influenza strains (A H3N2 Sydney and B Yamanashi). Bars represent medians for each group. Asterisks (*) indicate significant differences from baseline. (A) Total ELISPOT responses representing all PBMCs; (B) CD8 ELISPOT responses representing CD8 cells only. There were significant decreases in total ELISPOT responses against influenza strains A H3N2 Wyoming and B Jilin at 4 weeks after vaccination (p ≤ 0.03). All other total and CD8 ELISPOT responses were not significantly different from baseline.

FIG. 3.

Comparison of ELISPOT decreases of LAIV and TIV recipients from baseline to week 4 after vaccination and from baseline to week 24 after vaccination. Data were derived from 85 and 90 HIV-infected TIV and LAIV recipients, respectively. Bars represent median differences from study week 0 to week 4 or 24. Asterisks (*) indicate significant differences between treatment groups. There were significantly larger differences in total and CD8 ELISPOT responses to all influenza strains in the seasonal vaccine of TIV vs. LAIV recipients (p ≤ 0.02).