CYTOKINE AND ANTIBODY RESPONSES TO MALARIA VACCINE CANDIDATE ANTIGENS, PLASMODIUM FALCIPARUM GLUTAMATE RICH PROTEIN (GLURP) AND MEROZOITE SURFACE PROTEIN (MSP3) IN GHANAIAN CHILDREN

ABSTRACT

GLURP and MSP3 are targets for antibodies involved in antibody-dependent cellular inhibition that may lead to protective immunity against malaria. Comparative assessment of IgG and subclass responses to GLURP and MSP3 in relation to immunity against malaria will provide relevant information that will be useful in future malaria vaccine development. Several studies have led to the recent recognition of the importance of T- cell in the generation of long-term antibody responses in malaria infection. Therefore, cellular responses to GLURP and MSP3 must be investigated to get a better understanding of the roles the various cytokines play in conferring immunity against 

malaria. The antibody responses to GLURP and MSP3 were measured by Enzyme-linked immunosorbent assay (ELISA) in samples obtained from a cohort of 300 children, 3-15 years of age. The plasma samples came from a previous longitudinal morbidity survey carried out over a period of 18 months (1994-1995) covering two malaria transmission seasons, in which children were classified as susceptible or resistant to malaria. In addition, peripheral blood mononuclear cells (PBMC’s) were stimulated in culture with GLURP peptides and cytokines were measured.The pattern of IgG subclass responses to both antigens was similar, indicating higher prevalence for cytophilic antibodies than non-cytophilic antibodies. The association between antibody levels and protection was statistically significant for GLURP IgG (P=0.001) for both GLURP and MSP3. However, when the effect of age was adjusted for in a logistic regression model, GLURP IgG and IgGl responses were associated with protection in Ghanaian children. For cellular responses to GLURP peptides, higher cytokine responses were raised in antigen-stimulated cultures of exposed individuals than in non-exposed individuals. The study found no significant association between cytokine responses in protected Ghanaian children and those susceptible to malaria (p>0.05). Furthermore, there was no correlation between antibody and cytokine responses in Ghanaian children.These results confirm the association between cytophilic antibodies against GLURP and MSP3 and protection from clinical malaria. The complementarity of antibodies responses against both antigens supports their use as a hybrid in a future malaria vaccine. The study showed cytokine responses against some GLURP peptides, suggesting that there are T- cell epitopes within the antigen. The knowledge of the level of cellular and antibody responses to GLURP and MSP3 of P. falciparum, and possibly the combined effect of these two antigens will be very useful in future malaria vaccine development.