Developing a multicomponent malaria vaccine: immunological and genetic analysis of selected plasmodium falciparum surface proteins
Ohas, Eunita Atieno
MetadataShow full item record
Vaccination is an attractive method for preventing and controlling malaria. Clinical and experimental data support the feasibility of developing an effective malaria vaccine. A number of plasmodial surface antigens have been identified and characterized as suitable vaccine candidates. However, it is now apparent that malaria vaccine development may be compromised by antigens variation. In the same context, through vaccine candidate antigens are being studied separately for antigenicity and immunogenicity, future vaccines will certainly included antigen mixtures. In this study, effects of antigenic variation on proliferative responses to the circumsporozoite protein (CSP) T cell epitopes 361-380 (TH3R epitope of the CSP), 368-390 (CTL epitope of the CSP) and cellular and humoral recognition of Transmission blocking vaccine 25H (TB V25H) and yeast expressed Plasmodium falciparum sexual stage antigen (yPfs28) were determined in persons naturally exposed to malaria. The CSP is known to be very variable whereas sexual stage antigens are fairly conserved. Thus, two aims were addressed in this study. The first aim was to establish the effect of antigenic variation on immunologic recognition of the Th 3R epitope and the variants of the CTL epitope. The second one was to determine immunologic recognition of TB V25 H and yeast expressed forms of P fs, (yPfs28) in persons naturally exposed to malaria and finally determine the extent of genetic variation on Pfs28. These phenomena were correlated with the end point of infection. To address the first aim, resistance to infection by Plasmodium falciparum in Kenyan study subjects, was correlated with proliferative response to CS peptides by peripheral blood lymphocytes. The results obtained here showed that of the 60 people tested, 87.5% recognized one or more of the variants tested. Furthermore, of those responding to the test antigens, a significant proportion (p<0.05) of the susceptible compared to the resistant group of persons recognized the variants, suggesting that the resistant cohort was probably protected by alternative immunologic responses such as cytokine production. In part two of the study, using PCR-based techniques, it was found that Pfs28 was conserved among field isolates, other than a truncated from of the gene which was co-amplified from parasite DNA in 5-10% of the samples, probably due to a deletion of the nucleotide sequence encoding the first EGF-like domain. Sera from frequently exposed individuals did not demonstrate antibody recognition of either TBV25H or Pfs28 at levels above that of naive sera. However, PBMC frequently proliferated in response to both TBV25H (28/81) and Pfs28(28/81) while a control yeast-expressed protein, Pv 200, elicited responses only infrequently (3/30). The results demonstrate that antigenic variation may alter immunologic recognition in resistant persons and support parasite survival. Secondly, that sexual stage antigens are able to stimulate T cell recognition suggesting that they or some cross.
- MST-Zoological Sciences