A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults.

Abstract

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 IIa 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 × 10(7) plaque-forming units of MVA85A. Specific T-cell responses were characterized by IFN-γ 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-γ, tumor necrosis factor-α, 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.

• Authors: Thomas J Scriba, Michele Tameris, Erica Smit, Linda van der Merwe, E Jane Hughes, Blessing Kadira, Katya Mauff, Sizulu Moyo, Nathaniel Brittain, Alison Lawrie, Humphrey Mulenga, Marwou de Kock, Lebohang Makhethe, Esme Janse van Rensburg, Sebastian Gelderbloem, Ashley Veldsman, Mark Hatherill, Hendrik Geldenhuys, Adrian V S Hill, Anthony Hawkridge, Gregory D Hussey, Willem A Hanekom, Helen McShane, Hassan Mahomed
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 185 Issue 7 Pg. 769-78 (Apr 01 2012) ISSN: 1535-4970 [Electronic] United States
• PMID: 22281831 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MVA 85A
• Tuberculosis Vaccines
• Vaccines, DNA
• Viral Vaccines

Topics

• AIDS-Related Opportunistic Infections (prevention & control)
• Adolescent
• Adult
• CD4 Lymphocyte Count
• Female
• HIV Infections (immunology)
• Humans
• Immunity, Cellular
• Male
• Middle Aged
• Tuberculosis Vaccines (adverse effects, immunology, therapeutic use)
• Tuberculosis, Pulmonary (immunology, prevention & control, therapy)
• Vaccines, DNA
• Viral Load
• Viral Vaccines (adverse effects, immunology, therapeutic use)
• Young Adult