Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Immunologic work up of subjects who didn't respond appropriately to a rabies post exposure prophylaxis

Background New recommendations for rabies postexposure prophylaxis (rPEP) were published by the Centers for Disease Control and Prevention and the World Health Organization in 2010. In view of these new recommendations, the adequacy of rPEP among patients consulting the travel clinic of the University Hospital of Lausanne has been investigated and 6,8% of patients have been identified as non-responders with the new rPEP regimen. In this study we have selected the non-responders for a complete immunologic work up. Method Clinical and paraclinical immunologic investigations have been done to the non- responders patients. Those investigations have been conducted to look for an increased susceptibility to infections and an immunodeficiency. The investigations included a clinical evaluation, a full blood count, measurement of the immunoglobulin levels, a numeration of the subpopulations of the lymphocytes, a HIV test and an evaluation of the humoral response to tetanus, pneumococcal, and hepatitis B vaccinations. A lymphocyte proliferation assay with rabies antigen was performed to assess the cellular immune response. Results 9 subjects with rabies antibody titers ≤0,5 IU/ml after an rPEP with 4 doses were included in this study (=non-responders). 8/9 of these non-responders had an unremarkable medical history. 9/9 of them had normal paraclinical tests that did not suggest an immunodeficiency. The results of the lymphocyte proliferation assay with rabies antigen showed a significant correlation between the level of the humoral and cellular response. Conclusion These results suggest that a 4 dose intramuscular rPEP elicits in some patients a relatively poor humoral and cellular response, even in the absence of any immunosuppression. A serology on day 21 of the rPEP seems therefore useful to identify the patients who don't respond appropriately. Those non-responders should receive additional doses until they reach an antibody titer above 0.5 IU/ml.