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First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment
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 st...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963980/ https://www.ncbi.nlm.nih.gov/pubmed/31683812 http://dx.doi.org/10.3390/vaccines7040166 |
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author | Vasina, Daria V. Kleymenov, Denis A. Manuylov, Victor A. Mazunina, Elena P. Koptev, Egor Yu. Tukhovskaya, Elena A. Murashev, Arkady N. Gintsburg, Alexander L. Gushchin, Vladimir A. Tkachuk, Artem P. |
author_facet | Vasina, Daria V. Kleymenov, Denis A. Manuylov, Victor A. Mazunina, Elena P. Koptev, Egor Yu. Tukhovskaya, Elena A. Murashev, Arkady N. Gintsburg, Alexander L. Gushchin, Vladimir A. Tkachuk, Artem P. |
author_sort | Vasina, Daria V. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6963980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69639802020-01-27 First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment Vasina, Daria V. Kleymenov, Denis A. Manuylov, Victor A. Mazunina, Elena P. Koptev, Egor Yu. Tukhovskaya, Elena A. Murashev, Arkady N. Gintsburg, Alexander L. Gushchin, Vladimir A. Tkachuk, Artem P. Vaccines (Basel) Article 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. MDPI 2019-11-01 /pmc/articles/PMC6963980/ /pubmed/31683812 http://dx.doi.org/10.3390/vaccines7040166 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vasina, Daria V. Kleymenov, Denis A. Manuylov, Victor A. Mazunina, Elena P. Koptev, Egor Yu. Tukhovskaya, Elena A. Murashev, Arkady N. Gintsburg, Alexander L. Gushchin, Vladimir A. Tkachuk, Artem P. First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title | First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title_full | First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title_fullStr | First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title_full_unstemmed | First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title_short | First-In-Human Trials of GamTBvac, a Recombinant Subunit Tuberculosis Vaccine Candidate: Safety and Immunogenicity Assessment |
title_sort | first-in-human trials of gamtbvac, a recombinant subunit tuberculosis vaccine candidate: safety and immunogenicity assessment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963980/ https://www.ncbi.nlm.nih.gov/pubmed/31683812 http://dx.doi.org/10.3390/vaccines7040166 |
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