Within the international PRIBOMAL consortium, Crucell is participating in pre-clinical studies towards an affordable, safe and efficacious two-component pediatric malaria vaccine. The aim of this project is to demonstrate feasibility (safety and efficacy) in pre-clinical studies of a novel, affordable, two-component, pediatric malaria vaccine.

Malaria is one of the major public health challenges in the world, causing more than one million deaths each year. The disease affects primarily children of the developing world, and it is understood to be both a disease of poverty and a cause of poverty. The available measures, such as personal protection or drugs, have proven insufficient to control the disease. A safe, affordable and efficacious pediatric malaria vaccine, which fits in the existing WHO Expanded Program on Immunization, would solve tremendous suffering to human kind.

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 an industrially developed, recombinant adenoviral vector carrying the identical P. falciparum antigens as the rBCG-based malaria vaccine.

Although no vaccine is available yet, studies using a truncated circumsporozoite (CS) protein of P. falciparum directly fused to the hepatitis B surface antigen, named RTS,S, has shown excellent safety and provided approximately 30-40% protection in human field trials in Africa. Such studies are extremely important because they demonstrate the feasibility of effective vaccination against P. falciparum, although RTS,S induced only limited memory T-cell responses and consequently the immune response lasted only for a short period.

It is now generally accepted that immunological control of P. falciparum will require a vaccine that induces both high level neutralizing antibodies as well as strong T-cell response. Hereto, many different technologies are currently being explored including vaccines based on synthetic peptides/proteins, recombinant DNA, recombinant viral vectors, and attenuated bacterial vectors.

Among all the technologies currently under development there are two systems, i.e. recombinant BCG (rBCG) and recombinant adenovirus (rAd), that stand out from the rest, based on their ability to elicit strong antigen-specific humoral and cellular host responses, and the availability of efficient production systems able to provide sufficient vaccine dosages for hundreds of millions in need. Crucell’s AdVac^® technology is currently being evaluated against, amongst others, poverty-related diseases malaria, tuberculosis and HIV. The two vaccine components will be assembled according to the latest developments in industrial and academic vaccine technology, which are considered as state of the art.

Malaria is one of today’s top three killers among communicable diseases. The disease currently represents one of the most prevalent infections in tropical and subtropical areas causing severe illness in 300 to 500 million individuals worldwide and causing one to three million deaths every year. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Unfortunately, mortality associated with severe or complicated malaria still exceeds 10-30%. Malaria is caused by the Plasmodium parasite and transmitted from person-to-person through the bite of a female Anopheles mosquito. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, this disease also affects travelers.