Keywords: Malaria, rBCG, rAd35, paediatric vaccine
Malaria is one of the major public health challenges in the world, causing more than one million deaths each year. The disease primarily affects children of the developing world. The available measures, such as personal protection or drugs, have proven insufficient to control the disease. A safe, affordable and efficacious paediatric malaria vaccine, which fits in the existing WHO Expanded Programme on Immunisation, would alleviate tremendous suffering in human kind.
Taking up this challenge, the PRIBOMAL consortium proposes to generate and test in preclinical models the safety and efficacy of an innovative malaria vaccine. The vaccine consists of a prime, to be administered at birth, of a novel recombinant BCG vector carrying preferentially multiple antigens derived from the Plasmodium falciparum parasite, the cause of malaria. The priming vaccine is followed at week 14 after birth by a booster vaccination using industrially developed, recombinant adenoviral vector carrying the identical Plasmodium falciparum antigens as the rBCG-based malaria vaccine.
Generation of these novel vaccine candidates as well as testing in established and novel pre-clinical models to determine potency and safety requires a combined European effort to bring together the required expertise on basic parasite biology, malaria epidemiology, disease onset and progression, recombinant vector technology, fundamental immunology, advanced animal models, and sophisticated proteomics. The international PRIBOMAL consortium bundles all required experience and as such is well positioned to successfully conduct this research programme.
It is estimated that more than 300 million individuals suffer from acute disease caused by the malaria parasite and that more than 1 million people succumb to this disease each year. Malaria, which is highly endemic in sub-Saharan Africa, claims its victims predominantly among children with the peak incidence of clinical malaria and 90% of malaria deaths in children younger than 5 years.
The challenge faced by the PRIBOMAL consortium is to design a safe, affordable paediatric malaria vaccine that provides long lasting protection against malaria and that fits within the existing WHO Expanded Programme on Immunisation (EPI) as to not further complicate operational vaccination logistics. The first vaccination that children would receive is at birth with Bacille Calmette-Guérin (BCG) a live and attenuated strain of Mycobacterium bovis, which is currently the only available vaccine against tuberculosis. BCG has been globally used as the TB vaccine for decades and has proven to be safe in hundreds of millions of children. In recent years BCG receives additional attention as a potential vaccine vehicle.
The PRIBOMAL consortium considers that a booster immunisation will be required to achieve long-lasting protection. Therefore, a choice was made to boost the rBCG.malaria vaccine, given at birth either alone or in addition to classical BCG, with a recombinant adenoviral vector, carrying the identical P. falciparum derived antigens, at 14 weeks after birth, thus compliant with WHO EPI schedule. Like rBCG, replication deficient adenoviral vector has an excellent safety record with tens of thousands of patients receiving recombinant adenoviral vectors in diverse gene therapy and vaccination trials without adverse effects.
To ultimately eradicate malaria disease hundreds of millions of vaccine dosages will need to be manufactured at low cost per dose, given that countries in sub-Saharan Africa do not have the economic means to purchase expensive vaccines. The manufacture of rBCG follows the exact same protocols and procedures as established for BGC and guarantees that sufficient doses of rBCG malaria vaccine can be manufactured at a price per dose similar to BCG. Consortium member Crucell has extensive expertise in adenoviral vaccine manufacturing, employing a mammalian cell line, coded PER.C6., which can be cultured in suspension in large volumes Therefore, the PRIMOBAL consortium members consider the proposed two-component paediatric malaria vaccine to be affordable, thus applicable in developing countries such as sub-Saharan Africa.
To demonstrate feasibility (safety and efficacy) in preclinical studies of a novel, affordable, two-component, paediatric malaria vaccine.
The ultimate deliverable of this programme is an efficacious paediatric malaria vaccine candidate that will eventually be advanced to GMP development and clinical trials. Besides reaching this aim, the consortium expects that during the execution of this programme extensive knowledge will be gathered regarding immunological features of different vaccination schedules, in combination with information on their protective ability. This information will help elucidate correlates of protection and facilitate rational design of future malaria vaccines.
It can be envisioned that vaccines against other disease such as for instance HIV, TB or even cancer vaccine development can directly benefit from the PRIBOMAL research. Like malaria these diseases are considered to require vaccines that elicit strong humoral and cellular immune responses against a broad range of epitopes.
|Official Address||Other Information|
|2||Stefan Kaufmann||Max Planck Institute for Infection Biology
Department of Immunology
|Tel: + 49/30-28460-500/-506 |
Fax: + 49/30-28460-501
|3||Marita Troye-Blomberg||Stockholm University
Department of Immunology
Svante Arrheniusväg 16
S-106 91 Stockholm
|Tel: + 46 (0) 8164164
Fax: + 46 (0) 8157356
|4||Tom Van der Poll||Academic Medical Centre
University of Amsterdam
Laboratory of Experimental
1100 DD Amsterdam
|Tel: +31 (0) 20 5665910
Fax: +31 (0) 20 6977192
|5||Robert Sauerwein||Radboud University
Nijmegen Medical Centre
Nijmegen Centre for Molecular Life
6500 HB Nijmegen
|6||Henriette Skovgaard Andersen||ACE BioSciences A/S
5220 Odense SØ
|Tel: +45 6565 2121
Fax: +45 6565 2122
|7||Clemens Kocken||Biomedical Primate Research Centre
Lange Kleiweg 139
2280 GH Rijswijk
|Tel: +31 15 284 2699 |
Fax: +31 15 284 3999