BackgroundHeterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20–25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults.MethodologyWe conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5–17 months in a highly endemic malaria transmission area of Burkina Faso.ResultsChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290–387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression.ConclusionsThis study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting.Trial registrationClinicalTrials.gov NCT01635647.Pactr.org PACTR201208000404131.

Aims: The aim of this study is to assess the prevalence of hemoglobin abnormalities and G6PD deficiency and their respective influence on anemia occurring in less than five years old children with clinical P. falciparum malaria living in Burkina Faso. Study Design: The study was a cross-sectional survey with descriptive focus conducted from December 2010 to January 2013 in Saponé health district and from May to October 2011 in Banfora health district. Clinical and laboratory data were collected. Blood smears on slides for malaria diagnosis by microscopy, hemoglobin level and filter paper for the detection of human genetic factors were performed. Methodology: A total of 386 subjects from Saponé (131) and Banfora (255) were enrolled. DNA collected from each sample was extracted using chelex-100 method and the human genetic resistance factors background was assessed by RFLP-PCR.  Abnormal hemoglobin patients were classified as NonAA while AA was defined the normal hemoglobin. Results: In this study, 70.98% (274/386) were classified normal hemoglobin (AA) while 29.02% (112/386) of subjects were carrying at least one abnormal (NonAA) allele: 24.35%AC, 3.63% AS, 0.78%CC and 0.26%SC. G6PD deficiency was 9.59% (37/386) among which, 4.92% for male and 4.66% in female. However, this gender difference was not statistically significant (p=1.00). 319/367 (86.92%) of the patients were anemic (59.4% with moderate anemia and 20.98% with mild anemia). The prevalence of anemia in G6PD deficient subjects was 83.33% (of which 58.33% were moderate anemia and 22.22% mild anemia). The difference between types of hemoglobin (p=0.64) in the occurrence of anemia (AA 87.64% and Non AA 85.18%) was not statistically significant. Conclusion: This study showed that the prevalence of these genetic factors was relatively low among children with clinical falciparum malaria with high parasite density. In addition, these factors appear to have no effect on anemia.

BackgroundHeterologous prime-boost immunisation with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA)-vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in a UK adult phase IIa sporozoite challenge study, and in a trial in Kenyan adults.MethodsWe conducted the first phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63-MVA ME-TRAP in 700 healthy malaria exposed children aged 5–17 months in a highly malaria-endemic area of Burkina Faso.Participants were randomly assigned to received either ChAd63 ME-TRAP followed eight weeks later by MVA ME-TRAP or 2 doses of rabies vaccine. Monitoring of solicited adverse events was performed for seven days after each vaccination. Unsolicited adverse events were recorded until one month post each vaccination. Serious adverse events and malaria episodes were monitored throughout the study duration. Blood samples were collected at predefined timepoints to assess vaccine immunogenicity.ResultsChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses [median 326 SFU/106 PBMC (95% CI 290–387)]. However, non-significant low efficacy was observed against clinical malaria during the follow-up period, with efficacy against primary endpoint estimated by proportional analysis being 10.7% (95% CI: −44.2 to 44.7%) at sixth months post MVA ME-TRAP and 3.1% (95% CI −15.0 to 18.3; p=0.72) by cox regression.ConclusionThis study has confirmed ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in children and infants with prior exposure to malaria. No significant protective efficacy was observed in this highly endemic context.