Paradoxical Generalized Decrease of Influenza-Specific T-Cell Responses in HIV-Infected Children after Administration of Inactivated Influenza Vaccine and Sporadic Decrease after Live Attenuated Influenza Vaccine

Session VI – Weinberg, Adriana

Title of Contribution: Paradoxical Generalized Decrease of Influenza-Specific T-Cell Responses in HIV-Infected Children after Administration of Inactivated Influenza Vaccine and Sporadic Decrease after Live Attenuated Influenza Vaccine
Author(s): Adriana Weinberg1*, Lin-Ye Song2, Robert Walker3, Maria Allende3, Terence Fenton2, Sharon Nachman4, Julie Patterson-Bartlett1, Myron Levin1
Affiliation(s): 1U CO Denver, Aurora, CO; 2Harvard Sch Publ Health Ctr for Biostatistics in AIDS Res, Boston, MA; 3MedImmune, Inc, Gaithersburg, MD; 4Stony Brook NY State U, Stony Brook, NY

Background: Cold adapted influenza vaccine (CAIV) significantly reduces cases of influenza in immune competent children compared to trivalent inactivated influenza vaccine (TIV) during seasons when the vaccine and circulating viral strains are matched or not. We extended this immunological comparison of the two vaccines to HIV-infected children by studying their anti-influenza T-cell ELISPOT responses after immunization with CAIV or TIV. The CAIV used in this study has not been registered and is not available outside of the US. Methods: 243 HIV-infected children on HAART randomly received either CAIV or TIV. Blood was obtained at 0, 4 and 24 weeks post-immunization (wpi) for plasma HIV RNA and lymphocyte phenotypes in all participants and for anti-influenza T-cell responses in a subgroup of 175 subjects equally distributed between CAIV and TIV recipients. T-cell anti-influenza IFNγ-ELISPOT responses were measured in peripheral blood mononuclear cells (PBMC), with or without CD8+ T cell-depletion, after stimulation with the attenuated influenza vaccine viruses (A H3N2 Wyoming; A H1N1 New Caledonia; B Jilin) or with mismatched strains (A H3N2 Sydney; B Yamanashi). The contribution of CD8+ T cells to the influenza-specific response (CD8 ELISPOT) was calculated by subtracting the spot forming cells (SFC)/106 cells obtained with CD8-depleted PBMC from the SFC/106 cells obtained non-depleted PBMC (total ELISPOT).  Statistical significance was defined by p≤0.05. Results: At baseline, the median ELISPOT results were 156, 136 and 120 SFC/106 PBMC for A H1N1 New Caledonia, A H3N2 Wyoming and B Jilin, respectively; CD8+ T cells mediated the bulk of the response (median of 122 SFC/106 cells for A H3N2 Wyoming); and total and CD8 ELISPOT responses were similar in CAIV and TIV recipients except for responses to A H3N2 Wyoming, which were significantly higher in TIV recipients. At 4 and 24 wpi, total and CD8 ELISPOT results significantly decreased in TIV recipients (1.5- to 3-fold decreases compared to baseline). In CAIV recipients, total ELISPOT responses to A H3N2 Wyoming and B Jilin significantly decreased at 4 wpi (<1.5-fold decreases). ELISPOT responses to other viruses and at other time points did not significantly change in CAIV recipients, including CD8 ELISPOT for A H3N2 Wyoming at 4 wpi. At 4 and 24 wpi total and CD8 ELISPOT responses against all vaccine-contained and mismatched influenza strains were significantly higher in CAIV vs. TIV recipients. ELISPOT responses to the vaccines were not influenced by age, gender, baseline CD4, plasma HIV RNA or baseline ELISPOT results. To exclude the potential effect of spurious, vaccine-unrelated factors to the paradoxical decrease in ELISPOT responses pi, we determined that PHA responses did not significantly decrease pi, and excluded clustering by time of blood collection or geographic location of the subjects with decreased ELISPOT responses pi. Conclusions: HIV-infected children had significant generalized decreases of influenza-specific T cell responses after immunization with TIV; there were fewer children with such decreases, and the decreases were not as marked, after administration of CAIV. The importance of these findings is unclear since non-HIV-infected children were not included in these studies.  Overall, influenza-specific ELISPOT responses were higher after CAIV compared with TIV in HIV-infected children.

Supported by MedImmune LLC.