title: Tailoring a Combination Preerythrocytic Malaria Vaccine.
abstract: The leading malaria vaccine candidate, RTS,S, based on the Plasmodium falciparum circumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, the Plasmodium berghei homologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Karolis
authors.initials: K
authors.lastname: Bauza
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom erwan.atcheson@seh.ox.ac.uk.
authors.forename: Erwan
authors.initials: E
authors.lastname: Atcheson
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Tomas
authors.initials: T
authors.lastname: Malinauskas
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blagborough
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Arturo
authors.initials: A
authors.lastname: Reyes-Sandoval
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins