Efficacy of Candidate Malaria Vaccines in Senegalese Adults
Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity with previous vector platforms.
Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).
The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies.
The investigators propose a Phase 2b study of 120 healthy adult men in Senegal. The investigators will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. The investigators also intend to assess the correlates of efficacy and natural immunity.
|Malaria||Biological: ChAd63 ME-TRAP and MVA ME-TRAP Biological: Rabies vaccine||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
|Official Title:||Efficacy Study of ChAd63-MVA ME-TRAP Prime-boost Vaccination Against Plasmodium Falciparum Infection|
- Vaccine Efficacy [ Time Frame: 18 weeks ]We will compare active and control vaccination for time to first episode of P.falciparum infection, defined as 2 or more consecutive blood samples confirmed positive by PCR, for P.falciparum.
- Vaccine immunogenicity [ Time Frame: 24 weeks ]
Measures of immunogenicity will include:
Ex vivo ELISPOT responses to overlapping pools of ME - TRAP peptides. 25 Cultured ELISPOT responses to overlapping pools of ME - TRAP peptides. ICS by flow cytometry for cell mediated immune responses ELISA for antibodies to malaria antigens All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities.
- Safety [ Time Frame: 24 weeks ]All solicited and unsolicited local and systemic vaccine- linked adverse events (AEs) including clinically significant laboratory abnormalities.
- Tertiary Endpoint - Metaanalysis of Vaccine Efficacy [ Time Frame: 24 weeks ]We will compare combined active vaccination from VAC046 and VAC047, with combined control vaccination from VAC046 and VAC047, for time to first episode of P.falciparum infection, defined as 2 or more consecutive blood samples confirmed positive by PCR for P.falciparum.
|Study Start Date:||August 2012|
|Study Completion Date:||February 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Active Comparator: ChAd63 ME-TRAP and MVA ME-TRAP
ChAd63 ME-TRAP / MVA ME-TRAP heterologous prime-boost immunisation
Biological: ChAd63 ME-TRAP and MVA ME-TRAP
ChAd63 ME-TRAP: 5 x 10^10vp MVA ME-TRAP: 2 x 10^8 pfu heterologous prime-boost immunisation
Placebo Comparator: Rabies vaccine
2 x 2.5IU Verorab
Biological: Rabies vaccine
2 x 2.5IU Verorab
Other Name: Verorab
Please refer to this study by its ClinicalTrials.gov identifier: NCT01658696
|University Cheikh Anta Diop (UCAD)|
|Dakar, Senegal, BP 5005|