METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.
RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.
CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.
RESULTS: A noticeable variation between the RDT (Alltest Biotech, China) and nPCR results was observed, for RDT 78% (46/59) were P. falciparum positive, 6.8% (4/59) were co-infected with both P. falciparum and Plasmodium vivax, 15.3% (9/59) were negative by the RDT. However, when the nPCR was applied only 44.1% (26/59) and 55.9% (33/59) was P. falciparum positive and negative respectively. The pfhrp2 was further amplified form all nPCR positive samples. Only 17 DNA samples were positive from the 26 positive P. falciparum, interestingly, variation in band sizes was observed and further confirmed by DNA sequencing, and sequencing analysis revealed a high-level of genetic diversity of the pfhrp2 gene in the parasite population from the study area. However, despite extreme sequence variation, diversity of PfHRP2 does not appear to affect RDT performance.
METHODS: Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.
RESULTS: The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.
CONCLUSION: Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.