Two Decades of Commitment to Malaria Vaccine Development: GlaxoSmithKline Biologicals

W. Ripley Ballou Global Clinical Research & Development, GlaxoSmithKline Biologicals, Rixensart, Belgium

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Conor P. Cahill Global Clinical Research & Development, GlaxoSmithKline Biologicals, Rixensart, Belgium

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GlaxoSmithKline Biologicals (GSK) is committed to the development of a safe and effective malaria vaccine. Its research program in this field was initiated in 1984 and has been continuously active to this day, making it unparalleled within the vaccine industry. Although it works in partnerships with several leading organizations from the public sector, this effort has required GSK to invest major financial and human resource commitments, and its partners rely heavily on the company’s global infrastructure and expertise in research, advanced clinical development, regulatory, large-scale manufacturing, and commercialization. Through GSK’s pioneering business model and working in partnership with global vaccine funding agencies, the company is committed to seeing that, once approved, a safe and effective malaria vaccine will be available to everyone that needs it.

Author Notes

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  • 28

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  • 41

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  • 42

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  • 43

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  • 44

    Schwenk R, Asher LV, Chalom I, Lanar D, Sun P, White K, Keil D, Kester KE, Stoute J, Heppner DG, Krzych U, 2003. Opsonization by antigen-specific antibodies as a mechanism of protective immunity induced by Plasmodium falciparum circumsporozoite protein-based vaccine. Parasite Immunol 25 :17–25.

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  • 45

    Sun P, Schwenk R, White K, Stoute JA, Cohen J, Ballou WR, Voss G, Kester KE, Heppner DG, Krzych U, 2003. Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4(+) and CD8(+) T cells producing IFN-gamma. J Immunol 171 :6961–6967.

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  • 46

    Kester KE, McKinney DA, Tornieporth N, Ockenhouse CF, Heppner DG, Hall T, Wellde BT, White K, Sun P, Schwenk R, Krzych U, Delchambre M, Voss G, Gasser RA, Dowler MG, O’Brien M, Wittes J, Wirtz R, Cohen J, Ballou WR for the RTS,S Malaria Vaccine Evaluation Group, 2007. A phase 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. Vaccine 25 :5359–5366.

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  • 47

    Doherty JF, Pinder M, Tornieporth N, Carton C, Vigneron L, Milligan P, Ballou WR, Kester KE, Voss G, Momin P, Greenwood BM, McAdam KPWJ, Cohen J, 1999. A Phase I safety and immunogenicity trial with the candidate malaria vaccine, RTS,S/SABAS2, in semi-immune adults in The Gambia. Am J Trop Med Hyg 61 :865–868.

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  • 48

    Bojang KA, Milligan PJM, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DC, Reece WH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill AVS, McAdam KP, Tornieporth N, Cohen JD, Doherty T, for the RTS,S Malaria Vaccine Trial Team, 2001. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358 :1927–1934.

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  • 49

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  • 50

    Alloueche A, Milligan P, Conway DJ, Pinder M, Bojang K, Doherty T, Tornieporth N, Cohen J, Greenwood BM, 2003. Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific. Am J Trop Med Hyg 68 :97–101.

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  • 51

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  • 52

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  • 53

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  • 54

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    Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR, 2005. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomized controlled trial. Lancet 366 :2012–2018.

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  • 56

    Stewart VA, Walsh DS, McGrath SM, Kester KE, Cummings JF, Voss G, Delchambre M, Garçon N, Cohen JD, Heppner DG, 2006. Cutaneous delayed-type hypersensitivity (DTH) in a multi-formulation comparator trial of the anti-falciparum malaria vaccine candidate RTS,S in rhesus macaques. Vaccine 24 :6493–6502.

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  • 57

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  • 59

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    Ockenhouse CF, Angov E, Kester KE, Diggs C, Soisson L, Cummings JF, Stewart AV, Palmer DR, Mahajan B, Krzych U, Tornieporth N, Delchambre M, Vanhandenhove M, Ofori-Anyinam O, Cohen J, Lyon JA, Heppner DG; MSP-1 Working Group, 2006. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine 24 :3009–3017.

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    Polhemus ME, Magill AJ, Cummings JF, Kester KE, Ocken-house CF, Lanar DE, Dutta S, Barbosa A, Soisson L, Diggs CL, Robinson SA, Haynes JD, Stewart VA, Ware LA, Brando C, Krzych U, Bowden RA, Cohen JD, Dubois MC, Ofori-Anyinam O, De-Kock E, Ballou WR, Heppner DG, 2007. Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvated with AS02A, in malaria-naive adults at the Walter Reed Army Institute of Research. Vaccine 25 :4203–4212.

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  • 63

    Angov E, Aufiero BM, Turgeon AM, Van Handenhove M, Ockenhouse CF, Kester KE, Walsh DS, McBride JS, Dubois MC, Cohen J, Haynes JD, Eckels KH, Heppner DG, Ballou WR, Diggs CL, Lyon JA, 2003. Development and pre-clinical analysis of a Plasmodium falciparum merozoite surface protein-1(42) malaria vaccine. Mol Biochem Parasitol 128 :195–204.

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    Pichyangkul S, Gettayacamin M, Miller S, Lyon JA, Angov E, Tongtawe P, Ruble D, Heppner DG, Kester KE, Ballou WR, Diggs CL, Voss G, Cohen JD, Walsh DS, 2004. Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1-42 formulated with novel adjuvants or with alum. Vaccine 22 :3831–3840.

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    Wang R, Epstein J, Charoenvit Y, Baraceros FM, Rahardjo N, Gay T, Banania JG, Chattopadhyay R, de la Vega P, Richie TL, Tornieporth N, Doolan DL, Kester KE, Heppner DG, Norman J, Carucci DJ, Cohen JD, Hoffman SL, 2004. Induction in humans of CD8+ and CD4+ T cell and antibody responses by sequential immunization with malaria DNA and recombinant protein. J Immunol 172 :5561–5569.

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    Epstein JE, Charoenvit Y, Kester KE, Wang R, Newcomer R, Fitzpatrick S, Richie TL, Tornieporth N, Heppner DG, Ockenhouse C, Majam V, Holland C, Abot E, Ganeshan H, Berzins M, Jones T, Freydberg CN, Ng J, Norman J, Carucci DJ, Cohen J, Hoffman SL, 2004. Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A. Vaccine 22 :1592–1603.

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    Dunachie SJ, Walther M, Vuola JM, Webster DP, Keating SM, Berthoud T, Andrews L, Bejon P, Poulton I, Butcher G, Watkins K, Sinden RE, Leach A, Moris P, Tornieporth N, Schneider J, Dubovsky F, Tierney E, Williams J, Heppner DG, Gilbert SC, Cohen J, Hill AV, 2006. A clinical trial of prime-boost immunisation with the candidate malaria vaccines RTS,S/AS02A and MVA-CS. Vaccine 24 :2850–2859.

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    Heppner DG Jr, Kester KE, Ockenhouse CF, Tornieporth N, Ofori O, Lyon JA, Stewart VA, Dubois P, Lanar DE, Krzych U, Moris P, Angov E, Cummings JF, Leach A, Hall BT, Dutta S, Schwenk R, Hillier C, Barbosa A, Ware LA, Nair L, Darko CA, Withers MR, Ogutu B, Polhemus ME, Fukuda M, Pichyangkul S, Gettyacamin M, Diggs C, Soisson L, Milman J, Dubois MC, Garcon N, Tucker K, Wittes J, Plowe CV, Thera MA, Duombo OK, Pau MG, Goudsmit J, Ballou WR, Cohen J, 2004. Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research. Vaccine 23 :2243–2250.

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    Stewart VA, McGrath SM, Dubois PM, Pau MG, Mettens P, Shott J, Cobb M, Burge JR, Larson D, Ware LA, Demoitié MA, Weverling GJ, Bayat B, Custers JH, Dubois MC, Cohen J, Goudsmit J, Heppner DG, 2007. Priming with an adenovirus 35-CS vaccine followed by RTS,S/AS01B boosting significantly improves immunogenicity to P. falciparum CS over either malaria vaccine alone. Infect Immun 75 :2283–2290.

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