[HTML][HTML] A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial
SL Okitsu, O Silvie, N Westerfeld, M Curcic… - PloS one, 2007 - journals.plos.org
SL Okitsu, O Silvie, N Westerfeld, M Curcic, AR Kammer, MS Mueller, RW Sauerwein…
PloS one, 2007•journals.plos.orgObjectives 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 …
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 …
Objectives
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.
Methodology/Principal Findings
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 µg 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.
Trial Registration
ClinicalTrials.gov NCT00400101
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