STUDY OF THE IMMUNE-RESPONSE AGAINST PEPT IDES DERIVED FROM ANTIGENS OF HEPATIC AND ERYTHROCYTE STAGES OF PLASMODIUM-FALCIPARUM

Individuals living in malaria transmission zones progressively acquire an immunity against Plasmodium falciparum. The conditions in which th is immunity is acquired are not well known for areas of low transmissi on such as the Highlands of Madagascar. In order to specify these cond itions, a longitudinal clinical follow-up of voluntary subjects living in Ankazobe has been carried out since 1992. Entomological studies ha ve also been carried out in he homes of these subjects so as to detect the parasitical inoculation rate. In 1993 and 1994, a closer look was taken at the lymphoproliferative responses of these subjects to pepti des derived from antigens of hepatic and eurthrocyte stages of P. falc iparum. By such means, subjects can be compared in terms of immunity a nd the vaccinal interest of molecules can be specified. Several antige ns were used for these proliferation tests: i) LSA 1 (Liver Stage Anti gen) is an antigen expressed by hepatic schizonts (GUERIN, MARCHAND an d DRUILHE, 1987). Four peptides were synthesized from the sequence of the molecule of 200 kD (LSA 41-J-ter-nR); ii) MSP3: this antigen expre ssed at the merozoite stage (OEUVRAY et al, 1994) was used either as r ecombined with beta-galactosidase or transferase glutathione, or in th e shape of synthetic peptides. Three peptides 210a, b, c, were studied . This antigen is particularly involved in the monocyte-antibody-paras ite interaction; iii) RESA antigen (Ring infected Erythrocyte Stage An tifen). Samples were taken from 66 subjects in 1993 and from 133 subje cts in 1994. The proportion of ''responding'' subjects for these molec ules were: a) for the LSA1 peptides: from 18 to 33 % according to pept ide, in 1993 6,7 to 16, 2 % in 1994; b) for MSP3: from 28 to 39 % in 1 993 and 14 to 32 % in 1994 (with very different responses for the same peptide, from 1993 to 1994); c) RESA: from 20 to 23 % according to ag e. In an area of low and seasonal transmission of malaria (5 infesting bites/man/year), the number of <<responding>> subjects was reduced, e specially for those from whom samples were taken in 1994. Despite this law rate of parasitical inoculation, it does seem possible for an imm unity to develop, notably against hepatic stages of the parasite.