title: A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine.
abstract: We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum. Following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. The vaccines were safe but interferon-γ ELISPOT responses were low compared to other poxvirus vectors, despite targeting multiple antigens. There was no vaccine efficacy as measured by delay in time to parasitaemia. A number of possible explanations are discussed, including the very large insert size of the polyprotein transgene.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Oxford, OX3 7LJ, UK. david.porter@paediatrics.ox.ac.uk
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Thompson
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Berthoud
authors.forename: Claire L
authors.initials: CL
authors.lastname: Hutchings
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Sumi
authors.initials: S
authors.lastname: Biswas
authors.forename: Ian
authors.initials: I
authors.lastname: Poulton
authors.forename: Eric
authors.initials: E
authors.lastname: Prieur
authors.forename: Simon
authors.initials: S
authors.lastname: Correa
authors.forename: Rosalind
authors.initials: R
authors.lastname: Rowland
authors.forename: Trudie
authors.initials: T
authors.lastname: Lang
authors.forename: Jackie
authors.initials: J
authors.lastname: Williams
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.forename: Stephen
authors.initials: S
authors.lastname: Todryk
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D020815:Polyproteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D020815:Polyproteins; D015800:Protozoan Proteins; D022223:Vaccines, Subunit; D007371:Interferon-gamma