Safety of the RTS,S/AS02A malaria vaccine in Mozambican children during a Phase IIb trial

RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on the Plasmodium falciparum circumsporozoite surface antigen and is currently the most advanced malaria vaccine candidate in development. A proof of concept phase Ilb trial of the RTS,S/AS02A in Mozambican children aged 1-4 years determined a vaccine efficacy against risk of clinical malaria of 35.3% (95% CI 21.6-46.6; p < 0.0001) and against severe malaria of 48.6% (95% CI 12.3-71.0; p = 0.02). We evaluated the safety of the RTS,S/AS02A vaccine. 2022 children that received at least one vaccine dose of RTS,S/AS02A or control vaccines were included in the intention to treat safety analysis. Vaccine safety was evaluated using active and passive follow-up. Participants were observed for at least 1 h after each dose. Trained field workers visited children at home daily for the next 3 days to record solicited and unsolicited local and general symptoms. Investigators followed-up participants with severe adverse events until month 21. Overall, we recorded 1712 unsolicited adverse events after vaccination, 53% in the intervention and 47% in the control group. Most unsolicited adverse events reported with RTS,S/AS02A were self-limited, and participants recovered without sequelae. Local reactogenicity increased with the number of doses. The proportion of children experiencing serious adverse events was lower in the RTS,S/AS02A recipients compared to the control group (Engerix-B (TM) or Prevnar (TM) and Hiberix (TM)). Overall, these results indicate that the RTS,S/AS02A vaccine has a good safety profile and well tolerated when given in three doses to semi-immune children living in malaria-endemic areas. (c) 2007 Elsevier Ltd. All rights reserved.