Prophylactic Effect of a Therapeutic Vaccine against TB Based on Fragments of Mycobacterium tuberculosis

Cristina Vilaplana,Sergio Pinto,Jorge Díaz,Neus Cáceres,Pere-Joan Cardona,Olga Gil,Francesco Dieli

doi:10.1371/journal.pone.0020404

Abstract

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

Highlights

Despite the major efforts undertaken to eradicate tuberculosis (TB), it remains a major health problem, with approximately 1.8 million deaths, 9 million incident cases and 13 million prevalent cases worldwide every year [1]
The aim of the present project was to assess the protective capacity of the RUTIH vaccine given either as prophylaxis, or soon after the infection, i.e. before the onset of the infection induced immune response.Primarily designed as a therapeutic agent to shorten the chemotherapy treatment of latent tuberculosis infection (LTBI), RUTIH is developed under good manufacturing practices (GMP) in Badalona (Catalonia, Spain), by Archivel Farma [4]
RUTIH vaccine reduced the bacillary load in both lungs (0.58 log) and spleen (0.6 log) of mice, showing a statistically significant protective effect when compared to the control group (One-Way Anova, p,0.005)

Summary

Introduction

Despite the major efforts undertaken to eradicate tuberculosis (TB), it remains a major health problem, with approximately 1.8 million deaths, 9 million incident cases and 13 million prevalent cases worldwide every year [1]. One of the key priorities for tuberculosis research involves focusing on therapeutic and preventive strategies [2]. In order to stop the spread of this infection, most recent research has focused on designing new prophylactic vaccine candidates with better safety and immunogenic profiles to either boost BCG (by ameliorating its immunogenic profile and prolonging its protection), or replace it [3]. As numerous different aspects of TB need to be covered in order to achieve its final eradication [3], the ‘‘perfect’’ approach would appear to involve a single polyfunctional vaccine candidate that is able to prevent the infection of healthy individuals whilst at the same preventing the reactivation and reinfection of latently infected people. The aim of the present project was to assess the protective capacity of the RUTIH vaccine given either as prophylaxis, or soon after the infection, i.e. before the onset of the infection induced immune response.Primarily designed as a therapeutic agent to shorten the chemotherapy treatment of latent tuberculosis infection (LTBI), RUTIH is developed under good manufacturing practices (GMP) in Badalona (Catalonia, Spain), by Archivel Farma [4]

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Results

Conclusion