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Vaccine. 2015 Jul 9;33(30):3592-9. doi: 10.1016/j.vaccine.2015.05.036. Epub 2015 Jun 3.

The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial.

Author information

1
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
2
Aeras, Rockville, MD, USA.
3
Clinical Research-HIV Therapeutics Group, Gilead Sciences Inc, Foster City, CA, USA.
4
Statens Serum Institut, Copenhagen, Denmark.
5
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. Electronic address: Thomas.scriba@uct.ac.za.
6
Sanofi Pasteur, Swiftwater, PA, USA.

Abstract

BACKGROUND:

New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31 adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting.

METHODS:

In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis-uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500nmol IC31, two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays.

RESULTS:

Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ(+)TNF-α(+)IL-2(+) or TNF-α(+)IL-2(+) cells. These memory responses persisted up to the end of follow up, on study day 182.

CONCLUSIONS:

H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02075203.

KEYWORDS:

Adults; Clinical trial; H4:IC31; Mycobacterium tuberculosis; The trial was registered with the South African National Clinical Trials Register (number DoH 27-1108-2525) and ClinicalTrials.gov (NCT02109874); Vaccine

PMID:
26048780
DOI:
10.1016/j.vaccine.2015.05.036
[Indexed for MEDLINE]

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