A Phase IIa Trial of the New Tuberculosis Vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected Adults

被引：69

作者：

Scriba, Thomas J. ^{[1
,2
]}

Tameris, Michele ^{[1
,2
]}

Smit, Erica ^{[1
,2
]}

van der Merwe, Linda ^{[1
,2
]}

Hughes, E. Jane ^{[1
,2
]}

Kadira, Blessing ^{[1
,2
]}

Mauff, Katya ^{[3
]}

Moyo, Sizulu ^{[1
,2
]}

Brittain, Nathaniel ^{[4
]}

Lawrie, Alison ^{[4
]}

Mulenga, Humphrey ^{[1
,2
]}

de Kock, Marwou ^{[1
,2
]}

Makhethe, Lebohang ^{[1
,2
]}

van Rensburg, Esme Janse ^{[1
,2
]}

Gelderbloem, Sebastian ^{[5
]}

Veldsman, Ashley ^{[1
,2
]}

Hatherill, Mark ^{[1
,2
]}

Geldenhuys, Hendrik ^{[1
,2
]}

Hill, Adrian V. S. ^{[4
]}

Hawkridge, Anthony ^{[1
,2
]}

Hussey, Gregory D. ^{[1
,2
]}

Hanekom, Willem A. ^{[1
,2
]}

McShane, Helen ^{[4
]}

Mahomed, Hassan ^{[1
,2
]}

机构：

[1] Univ Cape Town, Inst Infect Dis & Mol Med, S African TB Vaccine Initiat, ZA-7925 Cape Town, South Africa

[2] Univ Cape Town, Sch Child & Adolescent Hlth, ZA-7925 Cape Town, South Africa

[3] Univ Cape Town, Dept Stat Sci, ZA-7925 Cape Town, South Africa

[4] Univ Oxford, Jenner Inst, Oxford, England

[5] Aeras, Rondebosch, South Africa

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2012年 / 185卷 / 07期

基金：

英国惠康基金;

关键词：

tuberculosis; HIV-1; vaccine; MVA85A; clinical trial; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; BCG VACCINATION; SOUTH-AFRICA; VIRAL LOAD; IMMUNOGENICITY; PROTECTION; SAFETY; METAANALYSIS; MENINGITIS;

D O I：

10.1164/rccm.201108-1548OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control. Objective To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb- and/or HIV-infected persons in a setting where TB and HIV are endemic. Methods: An open-label, phase ha trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 x 10(7) plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-gamma enzyme-linked immunospot and whole blood intracellular cytokine staining assays. Measurements and Main Results: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4(+) T cells, coexpressing IFN-gamma, tumor necrosis factor-alpha, and IL-2. Magnitudes of pre- and postvaccination T-cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of antiretroviral therapy on immunogenicity of MVA85A was observed. Conclusions: MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.

引用

页码：769 / 778

页数：10

共 40 条

[1] A multistage tuberculosis vaccine that confers efficient protection before and after exposure [J].