Preclinical efficacy and immunogenicity assessment to show that a chimeric Plasmodium falciparum UB05-09 antigen could be a malaria vaccine candidate.

Although it is generally agreed that an effective vaccine would greatly accelerate the control of malaria, the lone registered malaria vaccine Mosquirix™ has an efficacy of 30%-60% that wanes rapidly, indicating a need for improved second-generation malaria vaccines. Previous studies suggested that immune responses to a chimeric Plasmodium falciparum antigen UB05-09 are associated with immune protection against malaria. Herein, the preclinical efficacy and immunogenicity of UB05-09 are tested. Growth inhibition assay was employed to measure the effect of anti-UB05-09 antibodies on P. falciparum growth in vitro. BALB/c mice were immunized with UB05-09 and challenged with the lethal Plasmodium yoelii 17XL infection. ELISA was used to measure antigen-specific antibody production. ELISPOT assays were employed to measure interferon-gamma production ex vivo after stimulation with chimeric UB05-09 and its constituent antigens. Purified immunoglobulins raised in rabbits against UB05-09 significantly inhibited P. falciparum growth in vitro compared to that of its respective constituent antigens. A combination of antibodies to UB05-09 and the apical membrane antigen (AMA1) completely inhibited P. falciparum growth in culture. Immunization of BALB/c mice with recombinant UB05-09 blocked parasitaemia and protected them against lethal P. yoelii 17XL challenge infection. These data suggest that UB05-09 is a malaria vaccine candidate that could be developed further and used in conjunction with AMA1 to create a potent malaria vaccine.

Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon.

The association of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and essential hypertension has been reported but with controversial results in diverse populations in Asia and Europe, thereby suggesting a dependency on ethnicity. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and essential hypertension in a Cameroonian population (Bantu ethnic group) of the South West Region. Analysis of anthropometric and biochemical data in hypertensive and normotensive subjects revealed that age, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, serum total cholesterol, and triglycerides are independent risk factors for essential hypertension. Substitution of thymine for cytosine at position 667 of the MTHFR gene was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies were found to be 7.3% CC, 58.5% CT, and 34.1% TT for hypertensive subjects compared to 90.0% CC, 10.0% CT, and 0.0% TT for normotensives. Allele frequencies were obtained as 36.6% C and 63.4% T for hypertensive subjects and 95.0% C and 5.0% T for normotensive subjects. These results reveal that the T allele predisposes individuals to hypertension. Therefore, there is an association between variants of the MTHFR gene and hypertension in Cameroonian patients from the South West region.

Characterisation of a heparan sulfate proteoglycan homologue OvPG-1 from Onchocerca volvulus.

OBJECTIVE: To determine the role of an immunodominant antigen OvPG-1 in human onchocerciasis. DESIGN: Cross-sectional study of subjects living in three onchocerciasis endemic areas. SETTING: Mbonge and Tubah divisions of Western Cameroon and in Esmeralda Province of Ecuador. SUBJECTS: There were 94 and 99 subjects from the Cameroon rain forest and savannah respectively, and 83 endemic residents from Ecuador. RESULTS: The IgG2 anti-OvPG-1 responses of visually impaired and microfiladermic patients were significantly higher than for their age and sex matched counterparts with normal vision and no microfiladermia (p=0.024). Furthermore, the isotype specificity of anti-OvPG-I responses varied for the various onchocerciasis endemic zones. IgG1, IgG2, IgG3 and IgE levels correlated with the presence of microfilariae in Cameroon, but not in Ecuador. CONCLUSION: Increased IgG and IgE levels to the antigen OvPG-1 seem to correlate with the development of onchocercal eye pathology. The present results suggest that the OvPG1 is a dominant antigen of Onchocerca volvulus with a significant role in the pathogenesis of onchocerciasis.