Blood, spleen and liver samples were harvested to analyze the anti-CS antibody levels, CS-specific T cells responses and liver stage burden in all challenged mice.
In every instance the parasite liver stage burden was approximately 3 logs higher in antibody deficient CSP transgenic mice as compared to antibody deficient mice alone.
To compare the neutralizing activity of the antibodies, P. yoelii salivary gland sporozoites were incubated with pooled immune sera from the respective immunized groups and injected into naïve mice and the liver stage burden was evaluated.
We found that immunization with RAS or GAPs led to a reversal of protection by approximately 3 logs in CSP-transgenic, JhT mice (Fig 2A), as compared to liver stage burden of an identically immunized JhT mice.
The reduced liver-stage burden with AdM33 was reflected in the levels of blood-stage parasitemia on day 5 following challenge with 50 sporozoites.
Antimalarial factors that can reduce liver-stage burden, including bednets (Lengeler, 2004), immunogenetic risk factors (Hill et al., 1991), and the RTS,S/AS02 vaccine (Alonso et al., 2004), can ameliorate the severity of subsequent blood-stage infection in naturally exposed individuals.
An increase in sporozoite and liver stage parasite burden may decrease the prepatent period [12], [18], and a decrease in burden could increase the prepatent period.
This phenotypically rich resource will continue to enroll new subjects and encourage discovery of genomic and other biomarkers using state-of-the-art research technology to help stage disease burden and better individualize treatment selection.
Future research can harness clinically useful biomarkers using state-of-the-art research technology to help stage disease burden and better individualize treatment selection for patients with bipolar disorder.
Our data establish this quantitative real-time PCR assay to be a fast and reproducible way of accurately assessing liver stage parasite burden and vaccine efficacy in rodent malaria models.
