Safety, immunogenicity and risk-benefit analysis of rVSV-ΔG-ZEBOV-GP (V920) Ebola vaccine in Phase I-III clinical trials across regions.

To evaluate the risk-benefits balance of the rVSV-ΔG-ZEBOV-GP vaccine. We performed a systematic review to summarize data on safety, immunogenicity and efficacy. About 17,600 adults and 234 children received 11 different doses of the V920 vaccine ranging from 3000 to 100 million and 20 million plaque-forming units, respectively, during Phase I-III clinical trials. Cases of severe but transient arthritis were reported in about six and 0.08% of vaccinees in high-income countries (HICs) and low-middle-income countries (LMICs), respectively. The 20 million plaque-forming units dose yielded GP-specific antibody titres which peaked at day 28 with a pooled geometric mean titres of 2557.7 (95% CI: 1665.5-3934.2) versus 1156.9 (95% CI: 832.5-1649.2) but with similar seroconversion rates at 96% (95% CI: 87-100) versus 100% (95% CI: 90-100) for HICs and LMICs, respectively. Data from stringent Phase I-II clinical trials in LMICs and HICs and from the ring efficacy trials yielded a good risk-benefit balance of the V920 vaccine in adults, but also in children and pregnant and lactating women and HIV-infected people.

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001.