Induction of T helper type 1 and 2 responses to 19-kilodalton merozoite surface protein 1 in vaccinated healthy volunteers and adults naturally exposed to malaria.
Plasmodium falciparum malaria is a major cause of death in the tropics. The 19-kDa subunit of P. falciparum merozoite surface protein 1 (MSP-1(19)), a major blood stage vaccine candidate, is the target of cellular and humoral immune responses in animals and humans. In this phase I trial of MSP-1(19), immunization of nonexposed human volunteers with either of the two allelic forms of recombinant MSP-1(19) induced high levels of antigen-specific Th1 (gamma interferon) and Th2 (interleukin 4 [IL-4] and IL-10) type lymphokines. The adjustment of the antigen dose and number of immunizations regulated the level of specificity of immune responses and Th1/Th2 bias of responses induced by vaccination. Novel conserved and allelic T-cell epitopes which induced cross-strain immune responses were identified. Importantly, responses to many of these novel epitopes were also present in adults exposed to malaria, both in east (Kenya) and west Africa (The Gambia). These data suggest that epitope-specific naturally acquired MSP-1(19) immune responses in endemic populations can be boosted by vaccination.
Lee
Edwin A M
EA
Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. elee@enterprise.molbiol.ox.ac.uk
Palmer
Dupeh R
DR
Flanagan
Katie L
KL
Reece
William H H
WH
Odhiambo
Kennedy
K
Marsh
Kevin
K
Pinder
Margaret
M
Gravenor
Michael B
MB
Keitel
Wendy A
WA
Kester
Kent E
KE
Diggs
Carter
C
Kaslow
David
D
Apostolopoulos
V
V
Ballou
W Ripley
WR
Hill
Adrian V S
AV
Krzych
Urszula
U
Plebanski
Magdalena
M
D000293:Adolescent; D000328:Adult; D019353:Endemic Diseases; D005714:Gambia; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007630:Kenya; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D021122:Protein Subunits; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D021122:Protein Subunits; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma