Impairment of tetanus-specific cellular and humoral responses following tetanus vaccination in human lymphatic filariasis

Abstract

To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-gamma) response in the EN group, in that they increased IFN-gamma production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-gamma responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10.

FIG. 1.

In vitro PBMC proliferative responses to BmA (A) and PHA (B) in EN individuals (n = 10), those with lymphedema or elephantiasis (CP; n = 10), and those with circulating microfilariae (MF; n = 10). Each dot represents an individual patient. Horizontal bars represent the GM of the SI of each group.

FIG. 2.

In vitro PBMC proliferative responses to TT prevaccination (A), following a single TT vaccination (B), or following two vaccinations (C). (A) Each dot represents an individual; horizontal bars represent the GM SI of each group. (B) Box-and-error bar plot of the percent change in TT-specific proliferation 6 months following a single TT vaccination. The horizontal bar represents the median, boxes represent the 25th and 75th percentiles, and vertical lines represent the 95th percentile. (C) TT-specific PBMC proliferative responses expressed as SI in the CP and MF groups before and 6 months after two doses of TT.

FIG. 3.

TT-specific IFN-γ levels before (A) and following (B) TT vaccination. (A) Data on net production of IFN-γ in vitro, with each dot representing a single individual and horizontal bars representing the GM of the group. (B) GM percent change in TT-specific IFN-γ levels 3 and 6 months post-TT vaccination compared with prevaccination levels.

FIG. 4.

IL-10 levels produced spontaneously and in response to TT prevaccination (A) and following TT vaccination (B). (A) Data on the spontaneous (Spon) and TT-specific IL-10 levels prevaccination, with each dot representing an individual. (B) GM percent change in TT-specific IL-10 levels 3 and 6 months post-TT vaccination compared with prevaccination levels.

FIG. 5.

Changes in antitetanus IgG isotype response levels at 6 months after TT vaccination. Data are represented as box-and-error bar plots of the percent change in TT-specific Ig1 (A), IgG2 (B), IgG3 (C), and IgG4 (D) isotypes 6 months following TT vaccination. Horizontal bar represent the median, boxes represent the 25th and 75th percentiles, and vertical lines represent the 95th percentile.