Angewandte Chemie International Edition

Cover image for Vol. 56 Issue 47

Editor: Neville Compton; Editor Emeritus: Peter Gölitz

Online ISSN: 1521-3773

Associated Title(s): Angewandte Chemie, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemistryOpen, ChemPhotoChem, ChemPlusChem, Zeitschrift für Chemie

Press Release

For full article and contact information, see Angew. Chem. Int. Ed. 2003, 42 (21), 2368 - 2371

No. 21/2003

New Hope for a Malaria Vaccine

Imitation malaria protein on viruslike particles
induces immune system to produce antibodies

Plasmodium falsiparum is a perfidious killer on whose account millions of human lives are lost every year. No cure has yet been found for this most pernicious malaria pathogen; many plasmodium strains have already developed resistance to conventional treatments. Researchers despairingly search for an effective vaccine against the parasite. The novel approach taken by a Swiss team could now be a step in the right direction.

The lifecycle of plasmodia is complex, passing back and forth between humans and mosquitoes. When a mosquito bites, the parasite is passed on in the form of sporozoites, which later lodge in the liver and pass through further developmental stages. A specific amino acid sequence in one surface protein on the sporozoites seems to be particularly well-suited as a point of attack for vaccines. It consists of a sequence of four amino acids that is repeated almost forty times. Scientists refer to this sequence as NPNA, a name taken from the abbreviations corresponding to the amino acids it contains. The research teams headed by J.A. Robinson from the University of Zurich, G. Pluschke from the Swiss Tropical Institute in Basel, and R. Zurbriggen from Pevio Biotech in Berne also took the NPNA approach. But in order to stabilize the spiral-like, twisted arrangement of the amino acid sequence, which is critical for later immunization, they had to fix it as a cyclical, peptidelike molecule. Such molecules, which emulate a structural element of a protein or peptide, are called peptide mimetics.

The decisive step in the route taken by the Swiss group was the combination of the NPNA peptide mimetic and the innovative virosome technology, developed by Pevion Biotech, a spin-off of the swiss companies Bachem and Berna Biotech. Virosomes are a type of liposome, which are tiny lipid bubbles. As well as lipid molecules, virosome membranes contain two proteins from influenza viruses and an antigen -- in this case, the NPNA peptide mimetic, which is presented on the virus surface by coupling it to a lipid molecule. The immune system reacts to virosomes in the same way as it would to a viral attack. Immune cells merge with the virosomes and then produce antibodies against the NPNA peptide mimetic. Initial trials in mice revealed that these antibodies also attack malaria sporozoites. This potential component of a vaccine, combined with several other already-developed peptide mimetics, must now prove its safety and effectiveness in clinical trials.