First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment.

Vasina Vasina,Gushchin Gushchin,Kleymenov Kleymenov,Tkachuk Tkachuk,Tukhovskaya Tukhovskaya,Murashev Murashev,Gintsburg Gintsburg,Koptev Koptev,Manuylov Manuylov,Mazunina Mazunina

doi:10.3390/vaccines7040166

Abstract

Tuberculosis is known to be the biggest global health problem, causing the most deaths by a single infectious agent. Vaccine-development efforts are extremely important. This paper represents the results of the first-in-human trial of recombinant subunit tuberculosis vaccine GamTBvac in a Phase I study. GamTBvac is a new BCG booster candidate vaccine containing dextran-binding domain modified Ag85a and ESAT6-CFP10 MTB antigens and CpG ODN adjuvant, formulated with dextrans. Safety and immunogenicity of GamTBvac were estimated in an open-label clinical trial on 60 Mycobacterium tuberculosis uninfected (MTB-uninfected) volunteers previously-vaccinated with Bacillus Calmette—Guérin vaccine (BCG). The candidate vaccine had an acceptable safety profile and was well-tolerated. Three different vaccine doses with a double-immunization scheme were assessed for immunogenicity and induced a significant increase in IFN-γ in-house IGRA response and IgG ELISA analysis. Among them, the half dose vaccine group (containing DBD-ESAT6-CFP10, 12.5 μg; DBD-Ag85a, 12.5 μg; CpG (ODN 2216), 75 μg; DEAE-Dextran 500 kDa, 250 μg; and Dextran 500 kDa, 5 mg) provided high, early and stable in time immune response specific to both protein antigen fusions and is proposed for the further studies.

Highlights

Despite an intensive global fight against tuberculosis (TB), annual World Health Organization (WHO) reports do not suggest that we are on a secure way of solving this problem
We report the results of a Phase I open-label clinical trial investigating the safety and immunogenicity of multi-subunit Bacillus Calmette—Guérin vaccine (BCG) booster candidate vaccine GamTBvac administered in Mycobacterium tuberculosis (MTB)-uninfected BCG-immunized volunteers living in Russia (Moscow region)
Results of antibody quantificationResults were of antibodyasquantification were expressed median fluorescence intensity (MFI). control

Summary

Introduction

Despite an intensive global fight against tuberculosis (TB), annual World Health Organization (WHO) reports do not suggest that we are on a secure way of solving this problem. The WHO has developed a global strategy and outlined targets for tuberculosis prevention, care, and control (WHO’s End TB Strategy) [1]. It is estimated that optimization of existing prevention and treatment methods could reduce incidence by 10%, while the development of new approaches would lead to a reduction to the expected 90% level by 2025 [2]. These estimates do not look realistic by the end of 2019; it does not mean that new TB vaccines are no longer needed.

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