Effect of adjuvant on reactogenicity and long-term immunogenicity of the malaria Vaccine ICC-1132 in macaques.
ICC-1132 is a malaria vaccine candidate based on a modified hepatitis B virus core particle (HBc) bearing putative protective epitopes from the circumsporozoite protein (CS) of Plasmodium falciparum. While the epitope carrier itself is immunogenic, its potency can be increased by formulation with adjuvants. As a prelude to Phase I clinical trials, rhesus macaques were immunised twice with GMP grade ICC--1132 in saline or formulated with the adjuvants Alhydrogel (Alhydrogel) or Montanide((R)) ISA 720 (Montanide). Both adjuvant formulations gave significant humoral responses after the first injection, with titres increasing further after the second dose. The Montanide formulation was the most immunogenic, but undesirable reactogenicity in the form of sterile abscesses was associated with higher dosage levels of ICC--1132. These side effects could be avoided with lower antigen load, or by formulation of the second dose in Alhydrogel. Such measures also reduced peak titres and longevity of antibodies against CS, demonstrating the delicate balance between immunogenicity and reactogenicity of new vaccine formulations.
Langermans
Jan A M
JA
Department of Parasitology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
Schmidt
Annette
A
Vervenne
Richard A W
RA
Birkett
Ashley J
AJ
Calvo-Calle
J Mauricio
JM
Hensmann
Meike
M
Thornton
George B
GB
Dubovsky
Filip
F
Weiler
Horst
H
Nardin
Elizabeth
E
Thomas
Alan W
AW
D000038:Abscess / Q000473:pathology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D023421:Models, Animal; D009829:Oleic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D009829:Oleic Acids; D015800:Protozoan Proteins; D014765:Viral Vaccines; C041595:circumsporozoite protein, Protozoan; C001681:mannide monooleate; D008353:Mannitol; D000536:Aluminum Hydroxide