Anti-influenza serum and mucosal antibody responses after administration of live attenuated or inactivated influenza vaccines to HIV-infected children

Abstract

Background: Live-attenuated influenza vaccine (LAIV) prevents more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the antibody responses to LAIV or TIV in HIV-infected children.

Methods: Blood and saliva obtained at enrollment, 4 and 24 weeks postimmunization from 243 HIV-infected children randomly assigned to TIV or LAIV were analyzed.

Results: Both vaccines increased the anti-influenza neutralizing antibodies at 4 and 24 weeks postimmunization. At 4 weeks postimmunization, TIV recipients had 2-fold to 3-fold higher neutralizing antibody titers than LAIV recipients, but the proportions of subjects with protective titers (≥ 1:40) were similar between treatment groups (96%-100% for influenza A and 81%-88% for influenza B). Both vaccines increased salivary homotypic IgG antibodies, but not IgA antibodies. Both vaccines also increased serum heterosubtypic antibodies. Among HIV-specific characteristics, the baseline viral load correlated best with the antibody responses to either vaccine. We used LAIV-virus shedding as a surrogate of influenza infection. Influenza-specific humoral and mucosal antibody levels were significantly higher in nonshedders than in shedders.

Conclusions: LAIV and TIV generated homotypic and heterosubtypic humoral and mucosal antibody responses in HIV-infected children. High titers of humoral or mucosal antibodies correlated with protection against viral shedding.

Figure 1

Neutralizing antibody (MN) responses to LAIV and TIV in HIV-infected children on HAART. Data were derived from 234 HIV-infected children randomly assigned to receive LAIV or TIV during the 2004–2005 influenza season. Bars represent geometric mean titers (GMT) and 95% CI. Baseline values were similar in both treatment groups. MN titers were significantly higher in TIV compared with LAIV recipients at weeks 4 and 24 for all strains except for A H1N1 New Caledonia at week 24 (F test).

Figure 2

Influenza-specific salivary IgG antibody responses to LAIV and TIV in HIV-infected children on HAART. Data were derived from 234 HIV-infected children randomly assigned to receive LAIV or TIV during the 2004–2005 influenza season. Bars represent geometric mean titers (GMT) and 95% CI. For the subjects who did not have detectable influenza-IgG in the saliva (N of 19, 7 and 6 at weeks 0, 4 and 24, respectively), an arbitrary value of 0.001 was used for the analysis. Baseline values were similar in both treatment groups. The increase from baseline in the influenza-IgG concentrations was significantly higher in TIV compared with LAIV recipients at week 4 (p=0.05; F test), but not at week 24 (p=0.12; F test).

Figure 3

Comparison of serum and salivary influenza-specific antibodies in HIV-infected LAIV recipients who excreted ≥1 vaccine viruses (shedders) or did not (non-shedders). Data were derived from 109 HIV-infected children on HAART who received LAIV 2004/2005 and had baseline antibody measurements. There were 22 influenza A H1N1 New Caledonia, 9 B Jilin and 3 A H3N2 Wyoming shedders. For the salivary influenza-IgG and IgA analyses, all shedders were analyzed together irrespective of the type of virus they shed. The F test was used for the statistical analysis.