Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli.

A recombinant Plasmodium falciparum glutamate-rich protein (GLURP) was produced in Escherichia coli as a nearly full-length protein. In order to map immunodominant regions on GLURP, the nonrepetitive amino-terminal region (R0) as well as the central repeat region (R1) and the carboxy-terminal repeat region (R2) were also produced as separate products. All four purified gene products reacted specifically with serum samples from adults living in an area of Liberia where malaria is holoendemic. It appears that the human immune response against GLURP is primarily directed against the R2 region because 94% of the serum samples reacted with this region in an immunoassay. Antibody reactivity against the R0 region was also observed in 75% of the serum samples, while the R1 region showed only weak antibody-binding activity. When the nearly full-length GLURP molecule was adsorbed to Al(OH)3 it was found to be immunogenic in mice. In these experiments, the antibody response was almost exclusively directed against the R2 region. When anti-GLURP sera were obtained from rabbits immunized with the three regions, R0, R1, and R2, respectively, they recognized in immunoprecipitation experiments authentic GLURP from P. falciparum grown in vitro. These results demonstrate that GLURP produced in E. coli can induce a humoral immune response against GLURP derived from blood-stage parasites

Immune responses to band 3 neoantigens on Plasmodium falciparum-infected erythrocytes in subjects living in an area of intense malaria transmission are associated with low parasite density and high hematocrit value.

During the intracellular development of the human malarial parasite, Plasmodium falciparum, cryptic regions of the erythrocyte band 3 protein are exposed. Antibodies against these band 3-related neoantigens block cytoadherence, and peptides based on amino acid sequences of putative exofacial loops of band 3 protein block the in vitro and in vivo adherence of P. falciparum-infected erythrocytes. At present, it is not known whether reactivity to these antigens is related to exposure to the malaria parasite or is correlated with protective immunity. The reactivities of plasma to peptides containing amino acid sequences of putative exofacial loops 3 and 7 of human band 3 protein were determined for children and adults living in an area of perennial malaria transmission (Liberia) and for donors who had never been exposed to malaria (Denmark). Plasma samples from children and adults living in an area of intense malaria transmission showed a much higher reactivity with the band 3 peptides than did those from nonimmune individuals. High reactivity to the loop 3 peptide (amino acids 546 to 555) was correlated with lower mean parasite density in children in the 5- to 9-year-old age group. The presence of antibodies against loop 3 and 7 peptides was not associated with a low packed erythrocyte volume (hematocrit); in fact, higher-than-average reactivities to both peptides were positively correlated with high hematocrit values, indicating that antibodies which specifically recognize the band 3-related neoantigens are not involved in hemolysis (autoimmunity)

Prolonged breast feeding, diarrhoeal disease, and survival of children in Guinea-Bissau.

OBJECTIVE--To analyse the impact of breast feeding on diarrhoeal disease and survival in children above 1 year of age in Guinea-Bissau, west Africa. DESIGN--A community study of an open cohort followed up weekly by interviews over 15 months. Data on feeding practices, anthropometry, and survival were recorded for three years. SETTING--301 randomly selected houses in a semiurban area in the capital, Bissau. SUBJECTS--849 children aged less than 3 years. MAIN OUTCOME MEASURES--Incidence and duration of diarrhoea, weight for age, and death of a child. RESULTS--The incidence of diarrhoea was higher in weaned children than in partially breast fed children, both in 1 year olds (relative risk 1.41; 95% confidence interval 1.23 to 1.62) and in 2 year olds (1.67; 1.29 to 2.15). The mean duration of an episode of diarrhoea was 5.3 days in breast fed children compared with 6.3 days in weaned children (P = 0.001). Independent of the age of weaning, a similar increase was found in an analysis comparing, for each child, the rate and duration of diarrhoea one month before and one month after weaning. Children with low weight for age were breast fed longer than the better nourished children (P = 0.02). Children aged 12-35 months who were not breast fed had a 3.5 times higher mortality (1.4 to 8.3) than breast fed children. CONCLUSIONS--The beneficial effects of breast feeding are not restricted to infancy. Though children who are partially breast fed after infancy may have a lower state of nutrition than the weaned ones, the benefit in terms of lower morbidity may be more important for child survival in places with a high morbidity from diarrhoea and with high mortality