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Infection and Immunity, March 2002, p. 1417-1421, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1417-1421.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Edwin A. M. Lee,^1* Dupeh R. Palmer,² Katie L. Flanagan,¹ William H. H. Reece,¹ Kennedy Odhiambo,³ Kevin Marsh,³ Margaret Pinder,⁴ Michael B. Gravenor,⁵ Wendy A. Keitel,⁶ Kent E. Kester,² Carter Diggs,⁷ David Kaslow,⁸ V. Apostolopoulos,⁹ W. Ripley Ballou,² Adrian V. S. Hill,¹ Urszula Krzych,² and Magdalena Plebanski^1,9

Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU,¹ Institute for Animal Health, Compton, Berkshire RG20 7NN, United Kingdom,⁵ Department of Immunology, Walter Reed Army Institute of Research,² Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, D.C.,⁷ KEMRI Centre for Geographical Medicine Research (Coast), Kilifi District Hospital, Kilifi, Kenya,³ Medical Research Council Laboratories, Fajara, Banjul, The Gambia,⁴ Department of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, Texas,⁶ Laboratory of Parasitic Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,⁸ Vaccines and Infectious Diseases Unit, The Austin Research Institute, Victoria 3084, Australia⁹

Received 18 April 2001/ Returned for modification 11 June 2001/ Accepted 24 October 2001

Plasmodium falciparum malaria is a major cause of death in the tropics. The 19-kDa subunit of P. falciparum merozoite surface protein 1 (MSP-1₁₉), 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-1₁₉, immunization of nonexposed human volunteers with either of the two allelic forms of recombinant MSP-1₁₉ 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-1₁₉ immune responses in endemic populations can be boosted by vaccination.

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* Corresponding author. Mailing address: Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. Phone: (44) 1865 222301. Fax: (44) 1865 221921. E-mail: elee{at}enterprise.molbiol.ox.ac.uk.

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Infection and Immunity, March 2002, p. 1417-1421, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1417-1421.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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