A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial.
OBJECTIVE
Peptides delivered on the surface of influenza virosomes have been shown to induce solid humoral immune responses in experimental animals. High titers of peptide-specific antibodies were also induced in a phase 1a clinical trial in volunteers immunized with virosomal formulations of two peptides derived from the circumsporozoite protein (CSP) and the apical membrane antigen 1 (AMA-1) of Plasmodium falciparum. The main objective of this study was to perform a detailed immunological and functional analysis of the CSP-specific antibodies elicited in this phase 1a trial.


RESULTS
46 healthy malaria-naïve adults were immunized with virosomal formulations of two peptide-phosphatidylethanolamine conjugates, one derived from the NANP repeat region of P. falciparum CSP (designated UK-39) the other from P. falciparum AMA-1 (designated AMA49-C1). The two antigens were delivered in two different concentrations, alone and in combination. One group was immunized with empty virosomes as control. In this report we show a detailed analysis of the antibody response against UK-39. Three vaccinations with a 10 microg dose of UK-39 induced high titers of sporozoite-binding antibodies in all volunteers. This IgG response was affinity maturated and long-lived. Co-administration of UK-39 and AMA49-C1 loaded virosomes did not interfere with the immunogenicity of UK-39. Purified total IgG from UK-39 immunized volunteers inhibited sporozoite migration and invasion of hepatocytes in vitro. Sporozoite inhibition closely correlated with titers measured in immunogenicity assays.


CONCLUSIONS
Virosomal delivery of a short, conformationally constrained peptide derived from P. falciparum CSP induced a long-lived parasite-inhibitory antibody response in humans. Combination with a second virosomally-formulated peptide derived from P. falciparum AMA-1 did not interfere with the immunogenicity of either peptide, demonstrating the potential of influenza virosomes as a versatile, human-compatible antigen delivery platform for the development of multivalent subunit vaccines.


BACKGROUND
ClinicalTrials.gov NCT00400101.
Molecular Immunology, Swiss Tropical Institute, Basel, Switzerland.
Shinji L
SL
Okitsu
Olivier
O
Silvie
Nicole
N
Westerfeld
Marija
M
Curcic
Andreas R
AR
Kammer
Markus S
MS
Mueller
Robert W
RW
Sauerwein
John A
JA
Robinson
Blaise
B
Genton
Dominique
D
Mazier
Rinaldo
R
Zurbriggen
Gerd
G
Pluschke
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D015153:Blotting, Western; D003429:Cross Reactions; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D022701:Virosomes / Q000276:immunology*
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D022701:Virosomes