Prevention of tuberculosis in bacille Calmette-Guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS

Infectious Disease and International Health, Dartmouth Medical School, Hanover, New Hampshire, USA.
AIDS (London, England) (Impact Factor: 5.55). 03/2010; 24(5):675-85. DOI: 10.1097/QAD.0b013e3283350f1b
Source: PubMed


To determine whether a multiple-dose series of an inactivated whole cell mycobacterial vaccine, Mycobacterium vaccae, can prevent HIV-associated tuberculosis.
The DarDar trial was a randomized, placebo-controlled, double-blind trial. The study was carried in an outpatient facility in Dar es Salaam, Tanzania. HIV-infected patients with CD4 cell counts of at least 200 cells/microl and a Bacille Calmette-Guérin scar were chosen for the study. The intervention was carried out by random 1:1 assignment to five intradermal doses of M. vaccae or placebo. Tuberculin skin tests were performed, and patients with reactions of at least 5 mm were administered isoniazid for 6 months. The main outcome measures were disseminated (primary endpoint), definite, and probable tuberculosis (secondary endpoints).
Two thousand thirteen individuals were randomized (1006 to M. vaccae, 1007 to placebo) and followed every 3 months for a median of 3.3 years. The trial was terminated early because of slow accrual of cases of disseminated tuberculosis and significant protection against definite tuberculosis. Hazard ratios were disseminated tuberculosis 0.52 (95% confidence interval 0.21-1.34; seven cases in M. vaccae, 13 cases in placebo; log-rank P = 0.16), definite tuberculosis 0.61 (95% confidence interval 0.39-0.96; 33 cases in M. vaccae, 52 cases in placebo; P = 0.03), and probable tuberculosis 1.17 (95% confidence interval 0.76-1.80; 48 cases in M. vaccae, 40 cases in placebo; P = 0.46). Immunization was well tolerated, with no adverse effect on CD4 cell count or HIV viral load, and no increase in the rate of serious adverse events.
Administration of a multiple-dose series of M. vaccae to HIV-infected adults with childhood Bacille Calmette-Guérin immunization is safe and is associated with significant protection against definite tuberculosis. These results provide evidence that immunization with a whole cell mycobacterial vaccine is a viable strategy for the prevention of HIV-associated tuberculosis.

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    • "peptide and a synthetic TLR - 9 agonist IIa Weinrich Olsen et al . 2001 ; van Dissel et al . 2010 ; Aagaard et al . 2011 ESAT - 6 Virulence factor Rv2660c Latency - associated protein RUTI Therapeutic N / A N / A Whole fragmented Mtb I Cardona 2006 Mycobacterium vaccae Therapeutic N / A N / A Whole killed mycobacteria III deBruyn and Garner 2010 ; von Reyn et al . 2010 ; Yang et al . 2011 Mycobacterium indicus pranii"
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    Cold Spring Harbor Perspectives in Medicine 06/2014; 4(6):a018523-a018523. DOI:10.1101/cshperspect.a018523 · 9.47 Impact Factor
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    • "Administration of various doses of MIP subsequent to TB chemotherapy seems to decrease the inflammatory responses and lead to amelioration of lung pathology in tested animal models (Gupta et al., 2012). M. vaccae administered in a multiple-dose series format promoted significant protection against TB in HIV-infected adults who have been vaccinated with BCG during childhood (von Reyn et al., 2010, 2012). Therefore this protocol represents a potential immunotherapeutic strategy against TB for a large population of patients that are co-infected with TB and HIV. "
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