The Tuberculin Skin Test Increases the Responses Measured by T Cell Interferon‐Gamma Release Assays

Abstract

RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non‐LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T‐cell interferon‐gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis‐related antigens (ESAT‐6, CFP‐10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post‐TST response even in non‐LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre‐TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.

QuantiFERON-TB Gold In-Tube Test for Tuberculosis Prevention in HIV-Infected Patients

“…Considering that TST may falsely elevate the baseline IFN-γ level in the IPT untreated patients (21), this could account for the significant reduction in levels (to normal range) observed despite non-compliance to LTBI treatment. The observed significant decline in IFN-γ level among immunocompetent individuals, despite non-compliance to LTBI treatment, may be explained by biological variation and ability of immunity to eradicate latent M. tuberculosis (20,22). However, this was not observed in either our study or a previous study on HIV-infected patients (15).…”

Vaccine against tuberculosis: what’s new?

“…Experimental data showed that RUTI® is safe and able to elicit T H 1-T H 2-T H 3 responses in animal models. Moreover, CD8 + T-cells and antibodies responses have been reported [85,87]. …”

Time interval to conversion of interferon-γ release assay after exposure to tuberculosis

“…However, the data regarding a boosting effect of the TST on IGRA assays are inconsistent across studies, and some previous studies confute a definite boosting of IGRA response by the TST [21][22][23].…”