BACKGROUND: RTS,S/AS02A, a pre-erythrocytic Plasmodium falciparum vaccine based upon the circumsporozoite protein, is the only vaccine demonstrated in field trials to confer partial protection against a range of malaria disease manifestations. Pre-clinical studies are on-going to identify new RTS,S formulations with improved magnitude and duration of specific immunity. METHODS: Rhesus macaques were immunized with saline or one of four "RTS,S/adjuvant" formulations at 0, 4, and 12 weeks: RTS,S/AS01B, RTS,S/AS02A-standard (current formulation), RTS,S/AS05 or RTS,S/AS06. An RTS,S/AS02A-accelerated group was immunized at 0, 1, and 4 weeks. Outcomes were safety, RTS,S-specific antibody, and IFN-gamma and IL-5 ELISpots (weeks 14 and 34). FINDINGS: All regimens were safe and, except for RTS,S/AS06, generated equivalent high titer antibody levels. For IFN-gamma ELISpots, RTS,S/AS01B had the highest geometric mean (GM) values at weeks 14 and 34, and was the only group with an overall GM mean (weeks 14+34) higher than RTS,S/AS02A-standard (p<0.015). For IFN-gamma to IL-5 ELISpot response ratios, RTS,S/AS01B had the highest values at weeks 14 and 34, and was the only group higher than RTS,S/AS02A-standard at each individual time point and overall (weeks 14+34) (p<0.015). INTERPRETATION: RTS,S/AS01B is a safe and immunogenically superior formulation for cellular responses, in comparison with the RTS,S/AS02A-standard. Phase 1, 2a, and 2b clinical trials are underway to determine if RTS,S/AS01B demonstrates improved immunogenicity and protective efficacy against experimental challenge and natural mosquito-borne malaria.
BACKGROUND: RTS,S/AS02A, a pre-erythrocytic Plasmodium falciparum vaccine based upon the circumsporozoite protein, is the only vaccine demonstrated in field trials to confer partial protection against a range of malaria disease manifestations. Pre-clinical studies are on-going to identify new RTS,S formulations with improved magnitude and duration of specific immunity. METHODS:Rhesus macaques were immunized with saline or one of four "RTS,S/adjuvant" formulations at 0, 4, and 12 weeks: RTS,S/AS01B, RTS,S/AS02A-standard (current formulation), RTS,S/AS05 or RTS,S/AS06. An RTS,S/AS02A-accelerated group was immunized at 0, 1, and 4 weeks. Outcomes were safety, RTS,S-specific antibody, and IFN-gamma and IL-5 ELISpots (weeks 14 and 34). FINDINGS: All regimens were safe and, except for RTS,S/AS06, generated equivalent high titer antibody levels. For IFN-gamma ELISpots, RTS,S/AS01B had the highest geometric mean (GM) values at weeks 14 and 34, and was the only group with an overall GM mean (weeks 14+34) higher than RTS,S/AS02A-standard (p<0.015). For IFN-gamma to IL-5 ELISpot response ratios, RTS,S/AS01B had the highest values at weeks 14 and 34, and was the only group higher than RTS,S/AS02A-standard at each individual time point and overall (weeks 14+34) (p<0.015). INTERPRETATION: RTS,S/AS01B is a safe and immunogenically superior formulation for cellular responses, in comparison with the RTS,S/AS02A-standard. Phase 1, 2a, and 2b clinical trials are underway to determine if RTS,S/AS01B demonstrates improved immunogenicity and protective efficacy against experimental challenge and natural mosquito-borne malaria.
Authors: S Pichyangkul; U Kum-Arb; K Yongvanitchit; A Limsalakpetch; M Gettayacamin; D E Lanar; L A Ware; V A Stewart; D G Heppner; P Mettens; J D Cohen; W R Ballou; M M Fukuda Journal: Infect Immun Date: 2007-10-22 Impact factor: 3.441
Authors: Kirsten E Lyke; Modibo Daou; Issa Diarra; Abdoulaye Kone; Bourema Kouriba; Mohamadou A Thera; Sheetij Dutta; David E Lanar; D Gray Heppner; Ogobara K Doumbo; Christopher V Plowe; Marcelo B Sztein Journal: Vaccine Date: 2009-01-31 Impact factor: 3.641
Authors: Seth Owusu-Agyei; Daniel Ansong; Kwaku Asante; Sandra Kwarteng Owusu; Ruth Owusu; Naana Ayiwa Wireko Brobby; David Dosoo; Alex Osei Akoto; Kingsley Osei-Kwakye; Emmanuel Asafo Adjei; Kwadwo Owusu Boahen; Justice Sylverken; George Adjei; David Sambian; Stephen Apanga; Kingsley Kayan; Johan Vekemans; Opokua Ofori-Anyinam; Amanda Leach; Marc Lievens; Marie-Ange Demoitie; Marie-Claude Dubois; Joe Cohen; W Ripley Ballou; Barbara Savarese; Daniel Chandramohan; John Owusu Gyapong; Paul Milligan; Sampson Antwi; Tsiri Agbenyega; Brian Greenwood; Jennifer Evans Journal: PLoS One Date: 2009-10-02 Impact factor: 3.240
Authors: John N Waitumbi; Samuel B Anyona; Carol W Hunja; Carolyne M Kifude; Mark E Polhemus; Douglas S Walsh; Chris F Ockenhouse; D Gray Heppner; Amanda Leach; Marc Lievens; W Ripley Ballou; Joe D Cohen; Colin J Sutherland Journal: PLoS One Date: 2009-11-17 Impact factor: 3.240
Authors: Mark E Polhemus; Shon A Remich; Bernhards R Ogutu; John N Waitumbi; Lucas Otieno; Stella Apollo; James F Cummings; Kent E Kester; Christian F Ockenhouse; Ann Stewart; Opokua Ofori-Anyinam; Isabelle Ramboer; Conor P Cahill; Marc Lievens; Marie-Claude Dubois; Marie-Ange Demoitie; Amanda Leach; Joe Cohen; W Ripley Ballou; D Gray Heppner Journal: PLoS One Date: 2009-07-31 Impact factor: 3.240