Mixed results with TB vaccines at the trial

Vaccination with a subunit candidate vaccine, or revaccination with the primary Bacillus Calmette-Guerin (BCG) vaccine, did not prevent the initial tuberculosis infection in South African adolescents in a high transmission zone compared with placebo, a phase II trial

Neither revaccination with BCG vaccine nor vaccination with H4: IC31, a subunit candidate vaccine, met the primary efficacy endpoints based on on QuantiFERON-TB Gold In-tube (QFT) conversion rates, reports Elisa Nemes, MD. However, adolescents who received either vaccine had a lower QFT conversion rate than patients receiving placebo (6.7% for BCG versus 8.1% for H4: IC31). versus 11.6% for placebo, respectively), they wrote in the New England Journal of Medicine .

The authors cited the potential drawbacks of the QFT test, namely "the variability of the baday and the uncertainty ng the most effective dosage threshold. However, they added that the research found recent infection, including that diagnosed by the QFT conversion, is linked to a higher risk of the disease.Moreover, studies in humans and at the same time are likely to be more common. animal suggest that a return to a negative tuberculin skin test is badociated with "early confinement of M tuberculosis infection and lower risk of tuberculosis".

We suggest that sustained QFT conversion is more likely to be a sustained infection M. tuberculosis and a higher risk of progression to disease than transient QFT conversion, "write the authors

candidate subunit vaccine, H4 : IC31 – which had shown protection in preclinical models and "acceptable safety and immunogenicity in humans" – in addition to revaccination with BCG vaccine Participants in this randomized clinical trial placebo-controlled trial were adolescents aged 12 to 17 who had received BCG vaccine in the & # 39; childhood and had tested negative for TB using the QFT and HIV [19659005]. receive the H4: IC31 vaccine, BCG or placebo revaccination. The median age of participants at departure was 14 years old, with 53% of girls and about two-thirds of the race or "Cape mixed ascendance" ethnicity.

Examination of primary results in a population with modified intent to treat% ( P = 0.63) for vaccine H4: IC31 versus 20.1% ( P = 0 , 29) for revaccination with BCG, according to the authors.

At least 550 participants who received at least one dose of experimental vaccine or placebo who reported at least one adverse event. Adverse events were mainly mild to moderate local injection site reactions. There were four serious adverse events – one in groups H4: IC31 and BCG and two in the placebo group – and 19 serious adverse events, but the author stated that none of them was judged to be vaccine-related. There was one suicide death in the placebo group.

Notably, revaccination with BCG vaccine was 45.4% effective P = 0.03) against sustained conversion of QFT, the authors added. The sustainability of this important finding and the potential significance of public health for protection against tuberculosis warrants epidemiological modeling and subsequent clinical evaluation.

The authors noted that estimates of efficacy against sustained QFT conversion for H4: IC31 vaccine (30.5%, P = 0.16) did not meet standard statistical criteria Efficacy, but as a predefined confidence interval of 80% had efficacy estimates ranging from 3.0 to 50.2%, they argued that subunit vaccines included few antigens. against M. tuberculosis may have a biological effect, a finding that encourages the clinical evaluation of vaccine candidates to subunits of the next generation. "

In addition to the technical limitations with QFT, the authors acknowledge Their findings have was limited by the fact that there is no definitive test for the acquisition, persistence or elimination of M. tuberculosis .

2018-07-11T17: 30: 00-0400