Abstract
This review describes the developmental history of the RTS,S/AS vaccine. Selection of the circumsporozoite protein (CSP) as the target antigen was key to the successful development of the vaccine so far, from concept to the initiation of Phase III testing. CSP, a pre-erythrocytic protective antigen against Plasmodium falciparum, has been demonstrated to be immunodominant and protective in pre-clinical studies both in animals and humans. The vaccine antigen was designated “RTS,S”; RTS being a hybrid polypeptide consisting of a portion of the CSP antigen and S the surface antigen of Hepatitis B virus (HBsAg). The RTS,S/AS candidate vaccine has been evaluated in multiple Phase I/II studies and shown to have a favourable safety profile and to be well tolerated in both adults and children. Consistent and significant efficacy against Plasmodium falciparum infection and disease was observed in the target population of infants and children in a range of age groups and in different malaria transmission settings. The RTS,S/AS01E malaria vaccine candidate has recently entered Phase III testing. Reaching this important milestone is the culmination of more than 20 years of research and development by GlaxoSmithKline, their partners and collaborators. If the Phase III results confirm the observations made during Phase II testing, the RTS,S/AS01E vaccine, when broadly implemented and judiciously integrated with other malaria-prevention measures, could have a major public-health impact in sub-Saharan Africa.
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Acknowledgments
The results reported in this review are the fruit of many years of very hard work by literally hundreds of highly dedicated individuals in research institutions and in organisations involved in the development of the RTS,S/AS malaria vaccine, in Europe, the USA, and Africa.
The authors wish in particular to acknowledge the many partner organisations that contributed to this work, including the Southern collaborating institutions: the Institut de Recherche en Science de la Santé, Nanoro, Burkina, the Kumasi Centre for Collaborative Research, Ghana, the School of Medical Sciences Kumasi, Ghana, the Kintampo Health Research Centre, Ghana, the Albert Schweitzer Hospital, Gabon, the Kenya Medical Research Institute, Kilifi, Kenya, the Wellcome Collaborative Research Programme, Kilifi, Kenya, the Kenya Medical Research Institute, Kisumu, Kenya, the University of North Carolina Project, Lilongwe, Malawi, the Centro de Investigação em Saude de Manhiça, Mozambique, the Ifakara Health Institute, Tanzania and the National Institute of Medical Research, Tanzania; and the Northern collaborating institutions: the Prince Leopold Institute of Tropical Medicine, Belgium, the University of Copenhagen, Denmark, the University of Tuebingen, Germany, the Bernhard Nocht Institute, Germany, the University of Barcelona, Spain, the Swiss Tropical Institute, Switzerland, the London School of Hygiene & Tropical Medicine, UK, the University of North Carolina at Chapel Hill, USA, the Walter Reed Army Institute of Research, USA, and the Center for Disease Control and Prevention, USA; the PATH Malaria Vaccine Initiative (PATH-MVI), the Malaria Clinical Trial Alliance (MCTA), and the Clinical Trial Partnership Committee (CTPC) which is a network of African-based research centres and Northern partners, PATH-MVI and GSK. The CTPC oversees the implementation of the RTS,S/AS clinical development plan. Most of all, the authors want to thank the thousands of volunteers who participated in the RTS,S/AS clinical trials, as well as their families and communities, for their trust and cooperation.
The authors would also like to acknowledge the significant contribution of Dr. Julia Donnelly for expert editorial assistance and Dr. Julie Harriague (4Clinics) for writing assistance.
Conflicts of Interest: J. Cohen, J. Vekemans, A. Leach and L. Schuerman are employees of GlaxoSmithKline Biologicals. A. Leach, J. Vekemans, J. Cohen, L. Schuerman and S. Benns hold shares in GlaxoSmithKline. J. Cohen is listed as an inventor of patented malaria vaccines, including RTS,S.
Comment of editor: In the mean time the clinical trial was successfully finished!
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Cohen, J., Benns, S., Vekemans, J., Leach, A., Schuerman, L. (2011). Development of the RTS,S/AS Vaccine Candidate from Concept to Phase III. In: Mehlhorn, H. (eds) Progress in Parasitology. Parasitology Research Monographs, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21396-0_7
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