Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection

PLoS One. 2014 Feb 26;9(2):e89612. doi: 10.1371/journal.pone.0089612. eCollection 2014.


Objectives: To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection.

Methods and findings: Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation.

Conclusion: This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase.

Trial registration: NCT01136161.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • HIV / isolation & purification
  • HIV Infections / complications
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Latent Tuberculosis / etiology*
  • Latent Tuberculosis / therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Safety
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis Vaccines / therapeutic use*
  • Vaccination


  • Tuberculosis Vaccines

Associated data


Grant support

As the owner and manufacturer of the vaccine to be studied (RUTI), Archivel Farma s.l. (Badalona, Catalonia, Spain) was the sponsor of this trial and funded it. Jordi Picas, Mercè Amat are employees of Archivel Farma S.L. Pere-Joan Cardona is consultant of Archivel Farma S.L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.