A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine

作者：White Michael T^*; Bejon Philip; Olotu Ally; Griffin Jamie T; Bojang Kalifa; Lusingu John; Salim Nahya; Abdulla Salim; Otsyula Nekoye; Agnandji Selidji T; Lell Bertrand; Asante Kwaku Poku; Owusu Agyei Seth; Mahama Emmanuel; Agbenyega Tsiri; Ansong Daniel; Sacarlal Jahit; Aponte John J; Ghani Azra C

来源：BMC Medicine, 2014, 12(1): 117.

DOI：10.1186/s12916-014-0117-2

• Malaria
• Vaccine
• Circumsporozoite protein
• Antibody
• RTS,S
• Phase 2 clinical trials
• Mathematical model
• Clinical immunity

The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria.
Methods: Using data from 5,144 participants in nine phase 2 trials, we explore predictors of vaccine immunogenicity (anti-CSP antibody titres), decay in antibody titres, and the association between antibody titres and clinical outcomes. We use empirically-observed relationships between these factors to predict vaccine efficacy in a range of scenarios.
Results: Vaccine-induced anti-CSP antibody titres were significantly associated with age (P = 0.04), adjuvant (P < 0.001), pre-vaccination anti-hepatitis B surface antigen titres (P = 0.005) and pre-vaccination anti-CSP titres (P < 0.001). Co-administration with other vaccines reduced anti-CSP antibody titres although not significantly (P = 0.095). Antibody titres showed a bi-phasic decay over time with an initial rapid decay in the first three months and a second slower decay over the next three to four years. Antibody titres were significantly associated with protection, with a titre of 51 (95% Credible Interval (CrI): 29 to 85) ELISA units/ml (EU/mL) predicted to prevent 50% of infections in children. Vaccine efficacy was predicted to decline to zero over four years in a setting with entomological inoculation rate (EIR) = 20 infectious bites per year (ibpy). Over a five-year follow-up period at an EIR = 20 ibpy, we predict RTS, S will avert 1,782 cases per 1,000 vaccinated children, 1,452 cases per 1,000 vaccinated infants, and 887 cases per 1,000 infants when co-administered with expanded programme on immunisation (EPI) vaccines. Our main study limitations include an absence of vaccine-induced cellular immune responses and short duration of follow-up in some individuals.
Conclusions: Vaccine-induced anti-CSP antibody titres and transmission intensity can explain variations in observed vaccine efficacy.

• 出版日期2014-7-10
• 单位河北医科大学