Efficacy of delayed, fractional dose RTS,S/AS01E malaria vaccine in adults in Kenya treated with artemisinin combination therapy plus primaquine

Objectives

The primary objectives is to assess vaccine efficacy assessed by time to first P. falciparum infection in RTS,S/AS01E vaccinated adults (Group 1) positive for P. falciparum by PCR at baseline and treated to clear parasites compared to adults administered a comparator vaccine (Group 4) positive for P. falciparum by PCR at baseline and treated to clear parasites.
Secondary Objectives:
1. To assess vaccine efficacy by time to first P. falciparum infection by PCR in RTS,S/AS01E vaccinated adults (Group 2) negative for P. falciparum at baseline and provided anti-malarial chemo-prophylaxis versus comparator group (Group 5) negative for P. falciparum at baseline and provided anti-malarial chemo-prophylaxis.
2. To assess the safety of RTS,S/AS01E in terms of serious adverse events (SAEs) during the whole study period (from Dose 1 to study conclusion)
3. To assess the safety and reactogenicity of RTS,S/AS01E in terms solicited local and systemic adverse events within 7 days after each vaccination in the first 50 subjects in groups 1 and 2, and in all 35 subjects from Group 3.
4. To assess the safety of RTS,S/AS01E in terms of unsolicited adverse events within 28 days after each vaccination Immunogenicity: To assess anti-circumsporozoite (CS) antibody titers & avidity, hepatitis B surface antibody (HBsAb) titers, from groups 1, 2 and 3 as detailed in Appendix E. Exploratory Objectives:
5. To assess in subjects immunized with RTS,S/AS01E the relationship between HLA Class 1 and Class 2 alleles with protection against P. falciparum infection.
6. To assess anti-rabies titers in a subset of subjects at time points from groups 4 and 5 as shown in Appendix E.
7. To assess cell-mediated immune responses and transcriptomes in Groups 1 – 3.