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Preliminary Preparation towards Malaria Vaccine Trials in Sri Lanka: Studies on Genetic Polymorphism and Immune Responses against the C-terminal Merozoite Surface Protein 1

Aresha MANAMPERI researcher laureate
amanamperi@yahoo.com

°1968 Sri Lanka
Master’s in biochemistry, molecular biology and gene technology, University of Colombo, Sri Lanka, 1997

Preliminary Preparation towards Malaria Vaccine Trials in Sri Lanka: Studies on Genetic Polymorphism and Immune Responses against the C-terminal Merozoite Surface Protein 1

Together with HIV and tuberculosis, malaria belongs to the top three of most frequently occurring infectious diseases. Over 90 % of the malaria cases occur in Subsaharan Africa (for instance Senegal), but India, Brazil and Sri Lanka carry a heavy burden too. In the latter country malaria constitutes the most important parasitic disease with an annual incidence of 300.000 new cases (on 18 million inhabitants). Two species of malaria parasites are important: Plasmodium vivax causes a serious febrile illness, but dangerous complications are rare. Infection with Plasmodium falciparum, on the contrary, can result in deadly complications, especially in young children and pregnant women. Both species are prevalent in the same areas of Sri Lanka and Senegal. Usually, they produce similar symptoms. It is possible to distinguish both species during microscopic diagnosis, but this requires quite some expertise. Nevertheless, a specific treatment is required for each parasite. Moreover, treatment is complicated, because of the increasing prevalence of resistance to the most common and less expensive drugs.
Vaccination with a vaccine that covers both parasites could constitute a solution to all these problems, but the development of a "universal vaccine" remains a challenge, due to the high variability of the protein structures between and within the two species (the so-called "genetic polymorphism"). One of the most promising parasitic proteins as candidate vaccine is the Merozoit Surface Protein-1 (MSP-1), which has a role in the penetration of the malaria parasite into the human red blood cells. Eliciting antibodies through vaccination with MSP-1 could partly protect mice and monkeys against malaria, but also in this case, the genetic variability prevented full and universal protection.
In preparation of clinical trials with candidate vaccines, Dr Manamperi carried out a number of field investigations in Sri Lanka and Senegal in order to characterise the variability of MSP1. She also showed that some parts of the protein remain constant even between P vivax and falciparum. In addition, she studied the nature of the antibodies, elicited by MSP-1 during natural infection in humans, as well as after vaccination in monkeys. This thorough and systematic investigation provides a strong basis to develop a "universal" malaria vaccine.
 

report by Prof. Dr. G. Vanham, Departement of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium