Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial |
| |
Authors: | Hermsen Cornelus C Verhage Danielle F Telgt Denise S C Teelen Karina Bousema J Teun Roestenberg Meta Bolad Ahmed Berzins Klavs Corradin Giampietro Leroy Odile Theisen Michael Sauerwein Robert W |
| |
Affiliation: | Department of Medical Microbiology 268, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. r.hermsen@ncmls.ru.nl |
| |
Abstract: | The glutamate-rich protein (GLURP) of P. falciparum is the target of cytophilic antibodies which are significantly associated with protection against clinical malaria. A phase 1 clinical trial was conducted in healthy adult volunteers with the long synthetic peptide (LSP) GLURP(85-213) combined with either Aluminum Hydroxide (Alum, 18 volunteers) or Montanide ISA 720 (ISA, 18 volunteers) as adjuvants. Immunizations with 10, 30 or 100 microg GLURP(85-213) were administered subcutaneously at days 0, 30, and 120. Adverse events occurred more frequently with increasing dosage of GLURP(85-213) LSP and were more prevalent in the ISA group. Serious vaccine-related adverse events were not observed. The vaccine induced dose-dependent cellular and humoral immune responses, with high levels of (mainly cytophilic IgG1) antibodies that recognize parasites by immunofluorescence (IFA). Plasma samples collected 30 days after the last immunization induced a dose-dependent inhibition of parasite growth in vitro in the presence of monocytes. In conclusion, immunizations with GLURP(85-213) LSP formulations induce adverse events but can be administered safely, generating antibodies with capacity to mediate growth-inhibitory activity against P. falciparum in vitro. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|