A phase I/IIa safety, immunogenicity, and efficacy bridging randomized study of a two-dose regimen of liquid and lyophilized formulations of the candidate malaria vaccine RTS,S/AS02A in malaria-naïve adults

Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research

“…This trial demonstrated a statistically significant association of anti-CSP antibody with prevention of parasitemia after malaria challenge. This confirms similar associations of anti-CSP antibody with protection in Phase 2a trials of adjuvanted RTS,S in malaria-naïve adults [12,13] and in a Phase 2b trial in malaria-experienced adults [14]. However, such association of anti-CS antibody with protection in Phase 2b trials of RTS,S/AS02A was not found in children [15,16] but was found in infants in malaria endemic Mozambique [17].…”

“…Observed efficacy was not different from that previously reported for two doses of RTS,S/AS02 administered at a 1-month interval [12,13] failing to suggest any benefit for a third dose of RTS,S/AS02 in terms of immediate protective efficacy against an experimental challenge. However, the present and previously reported Phase 2a trials, conducted in malaria-naïve volunteers, did not address the potential benefit of a third dose of RTS,S/AS02 on the duration of efficacy.…”

“…This trial was one in series of Phase 2a trials to explore the immunogenicity and efficacy of varying dose and schedule of intramuscular RTS,S/AS02 in malaria-naïve adults at WRAIR [11][12][13]. Although confidence intervals were broad, three doses of RTS,S/AS02 on the accelerated 0, 7, and 28 day schedule yielded no increase in immunogenicity or efficacy over the 0, 1, and 3 month schedule.…”

“…Although many candidate vaccines are in development [10], only the RTS,S antigen formulated with either the AS01 or the AS02 Adjuvant System consistently confers partial protective immunity against infection by the P. falciparum parasite in malaria-naive ( [11][12][13], Kester, unpublished) and malaria endemic populations ( [14,15], Polhemus, unpublished), and in one trial, reduced clinical and severe malaria in young African children for 18 months [15,16]. Most recently, RTS,S/AS02 given in an Expanded Programme on Immunization compatible schedule at 10, 14, and 18 weeks of age was shown for the first time to protect infants against infection and clinical malaria for a 3-month period [17].…”

The Impact of Immune Responses on the Asexual Erythrocytic Stages of Plasmodium and the Implication for Vaccine Development

“…Why bother developing blood stage vaccines? Extensive studies characterizing the leading pre-erythrocytic vaccine RTS,S have shown approximately 40% sterile protection of vaccinated US individuals (Kester et al, 2007). Protection in the field is restricted to reduced mortality and morbidity and requires vaccination of young children that have continued exposure to the parasite.…”