We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.
BackgroundThe World Health Organization (WHO) classifies Guinea-Bissau as having severe vitamin A deficiency (VAD). To date, no national survey has been conducted. We assessed vitamin A status among children in rural Guinea-Bissau to assess status and identify risk factors for VAD.MethodsIn a vitamin A supplementation trial in rural Guinea-Bissau, children aged 6 months to 2 years who were missing one or more vaccines were enrolled, vaccinated and randomized to vitamin A or placebo. Provided consent, a dried blood spot (DBS) sample was obtained from a subgroup of participants prior to supplementation. Vitamin A status and current infection was assessed by an ELISA measuring retinol-binding protein (RBP) and C-reactive protein (CRP). VAD was defined as RBP concentrations equivalent to plasma retinol <0.7 μmol/L; infection was defined as CRP >5 ml/L. In Poisson regression models providing prevalence ratios (PR), we investigated putative risk factors for VAD including sex, age, child factors, maternal factors, season (rainy: June-November; dry: December-May), geography, and use of health services.ResultsBased on DBS from 1102 children, the VAD prevalence was 65.7% (95% confidence interval 62.9-68.5), 11% higher than the WHO estimate of 54.7% (9.9-93.0). If children with infection were excluded, the prevalence was 60.2% (56.7-63.7). In the age group 9–11 months, there was no difference in prevalence of VAD among children who had received previous vaccines in a timely fashion and those who had not. Controlled for infection and other determinants of VAD, the prevalence of VAD was 1.64 (1.49-1.81) times higher in the rainy season compared to the dry, and varied up to 2-fold between ethnic groups and regions. Compared with having an inactivated vaccine as the most recent vaccine, having a live vaccine as the most recent vaccination was associated with lower prevalence of VAD (PR=0.84 (0.74-0.96)).ConclusionsThe prevalence of VAD was high in rural Guinea-Bissau. VAD varied significantly with season, ethnicity, region, and vaccination status.Trial registrationClinicaltrials.gov NCT00514891
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