The multicentre Phase III RTS,S vaccine trial

The only subunit vaccine thus far to demonstrate reproducible evidence of moderate protection in the field is the GlaxoSmithKline (GSK) Biologicals candidate RTS,S. The RTS,S vaccine is currently in a Phase III trial for licensure and has demonstrated an interim-analysis efficacy of 55.8% (97.5% CI, 50.6 to 60.4).

The RTS,S/AS01E Phase III vaccine trial (e-track 110021) includes two age cohorts (infants 6-12 weeks of age and children 5-17 months of age) recruited in Mozambique, Tanzania and Gabon. Eligible subjects were vaccinated with either: 1) a comparator, i.e., rabies vaccine or meningococcal C Conjugate vaccine depending on age group, 2) a course of RTS,S/AS01E. Primary vaccinations were given at study months 0, 1 and 2 (Figure 1). Children were then followed up for clinical malaria by passive case detection. This was carried out at the hospitals through morbidity surveillance systems to monitor attendances to the outpatient clinics and admissions to hospital. Parents/guardians of study participants were asked to take their children to the hospital should they have any health problem at any time, where they were managed and treated according to national guidelines by the attending medical personnel. If the axillary temperature was >37.5 ºC or there was a reported fever in the preceding 24 h, malaria parasitaemia was assessed.

The human CPS trial

An experimental model in which humans were inoculated with sporozoites under chloroquine prophylaxis (CPS), has demonstrated induction of high-level protection against homologous malaria challenge. The human CPS trial has been carried out in the context of single-centre randomized controlled trials. Enrolled volunteers received weekly CQ prophylaxis for a period of 3 months during which they were exposed thrice to 15 infected mosquitoes. Five to six months after discontinuation of CQ prophylaxis, all volunteers were challenged by the bites of 5 infectious mosquitoes to determine protection (Figure 2). This period was considered to be sufficient for CQ levels to drop below those that might be inhibitory to parasite multiplication. Individuals undergoing CQ prophylaxis only or exposed to uninfected mosquito bites served as infection controls during challenge. All subjects were checked daily on an outpatient basis from day 5 to day 21 after challenge for symptoms of malaria, and hematologic tests and peripheral blood smears were performed.

CONTACT

For questions or interest in our research, please, contact with:

Carlota Dobaño, PhD
Barcelona Centre for International Health Research (CRESIB)
Hospital Clínic de Barcelona
Universitat de Barcelona
Rosselló 132, 4th floor
08036 Barcelona, Spain
SysMalVac@cresib.cat