In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

BACKGROUND: DNA-based vaccines have been safe but weakly immunogenic in humans to date. METHODS AND FINDINGS: We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines. CONCLUSIONS: This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate. TRIAL REGISTRATION: ClinicalTrials.gov NCT00545987.

Incidence of tuberculosis and HIV and progression of silicosis and lung function impairment among former Basotho gold miners.

BACKGROUND: Pulmonary tuberculosis and HIV incidence, mortality, and the progression of silicosis and lung function impairment are described over a 1-year period in migrant ex-gold miners from Lesotho. METHODS: Seven hundred seventy-nine Basotho miners were followed for 1 year starting 18 months after lay-off from a South African gold mine in 1998. At baseline and follow-up, they underwent a respiratory symptom interview, physical examination, HIV test, chest radiograph, and spirometry. RESULTS: Five hundred thirteen of 779 (65.9%) participants attended both baseline and follow-up visits. HIV incidence was 5.4/100 person-years (95% CI: 3.4-8.2). Prevalence of silicosis (ILO score > or =1/1) was 26.6% at baseline and 27.0% at follow-up. Active tuberculosis diagnosed at baseline was a strong predictor of radiological progression of silicosis. Lung function as measured by FEV(1) declined an average of 91 ml between visits (95% CI: 67-116 ml). Calculated minimum incidence of tuberculosis was 3,085/100,000/years (95% CI: 1,797-4,940) at follow-up. Of those seen at baseline, 18 died before their scheduled follow-up visit (mean age: 51 years). CONCLUSIONS: High rates of mortality and of HIV infection and pulmonary tuberculosis were found in this cohort after leaving the South African goldmines. Continuing lung function loss was also apparent. A partnership between the South African mining industry and governments in labor-sending areas of Southern Africa is needed to provide continuity of care and access to HIV and tuberculosis treatment and prevention services. Active silicosis surveillance and an improved statutory compensation system are also needed. These findings can serve as a baseline against which the impact of such interventions can be assessed.