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Infection and Immunity, June 2005, p. 3587-3597, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3587-3597.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Safety and Enhanced Immunogenicity of a Hepatitis B Core Particle Plasmodium falciparum Malaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial

Giane A. Oliveira ,^1,, Kristiane Wetzel,^5, J. Mauricio Calvo-Calle,¹ Ruth Nussenzweig,¹ Annette Schmidt,⁵ Ashley Birkett,² Filip Dubovsky,³ Eveline Tierney,³ Christoph H. Gleiter,⁴ Gabriele Boehmer,⁴ Adrian J. F. Luty,⁶ Michael Ramharter,⁶ George B. Thornton,² Peter G. Kremsner,⁶ and Elizabeth H. Nardin^1*

Department of Medical Parasitology, New York University School of Medicine, New York, New York,¹ Apovia, Inc., San Diego, California,² Malaria Vaccine Initiative, Program for Appropriate Technologies in Health, Rockville, Maryland,³ Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany,⁴ Apovia, Inc., Martinsried, Germany,⁵ Institute for Tropical Medicine, Department of Human Parasitology, University of Tuebingen⁶

Received 2 August 2004/ Returned for modification 20 October 2004/ Accepted 25 January 2005

Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 µg or 50 µg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4⁺ T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.

Editor: J. D. Clements

G.A.O. and K.W. contributed equally to this study.

Present address: Regeneron Pharmaceuticals, Inc., Old Saw Mill River Road, Tarrytown, N.Y.

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