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.
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 mug or 50 mug 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.
Oliveira
Giane A
GA
Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.
Wetzel
Kristiane
K
Calvo-Calle
J Mauricio
JM
Nussenzweig
Ruth
R
Schmidt
Annette
A
Birkett
Ashley
A
Dubovsky
Filip
F
Tierney
Eveline
E
Gleiter
Christoph H
CH
Boehmer
Gabriele
G
Luty
Adrian J F
AJ
Ramharter
Michael
M
Thornton
George B
GB
Kremsner
Peter G
PG
Nardin
Elizabeth H
EH
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008353:Mannitol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000008:administration & dosage*; D010963:Plasmodium falciparum / Q000276:immunology*; D016037:Single-Blind Method
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D009829:Oleic Acids; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma