Pre–erythrocytic–stage immune effector mechanisms inPlasmodiumspp. infections

Abstract

The potent protective immunity against malaria induced by immunization of mice and humans with radiation–attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T–cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo . By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide–adjuvant vaccines, we have demonstrated that different T–cell–dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre–erythrocytic–stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity.

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine

“…The probability of this happening at random is 0.063. However, groups were small, and in only one of these comparisons were the differences statistically significant; D2-V vs. D2-D2 (P ϭ 0.02, 2 ). In the two experiments (Tables 1 and 2), 40 mice were ).…”

“…However, some of the mice in three other groups did not develop parasitemia (Table 1). There was also a statistically significant delay in onset of parasitemia in four other groups: D-P, V-V, P-D, and P-V (P Ͻ 0.0001, 2 . Based on a 24-hr cycle in erythrocytes and a 10-fold increase in parasitemia each cycle (average of 15 nuclei per each mature erythrocytic stage parasite), a one-day delay in onset of parasitemia would represent a 90% reduction in parasite burden.…”

“…This effort is in large part based on work in rodents that demonstrate that protective immunity induced by immunizing with irradiated sporozoites (2)(3)(4) or with DNA plasmids encoding Py proteins expressed in infected hepatocytes is eliminated by in vivo depletion of CD8ϩ T cells (5,6).…”

“…Only these two groups had statistically significant protection on day 14 as compared with the pooled controls (P Ͻ 0.0001, D-V; P ϭ 0.0006, D-D). All groups except the D-D group had significantly fewer protected mice than did the group primed with PyCSP DNA and boosted with NYVAC(K1L)-PyCSP (D-V) ( Table 1, P Ͻ 0.02, 2 ) and groups D-P, V-D, V-P, P-P, and P-D had significantly less protection (P Ͻ 0.05, 2 ) than did the D-D group. However, some of the mice in three other groups did not develop parasitemia (Table 1).…”

Antibody Response to Plasmodium Vivax Antigens in Fy-Negative Individuals From the Colombian Pacific Coast

“…1,2 Both innate factors and acquired immune responses protect humans from the clinical manifestations induced by multiplication of malaria parasites in the blood. 3,4 Of the multiple innate factors that protect individuals from malaria, hemoglobin abnormalities and lack of expression or modifications of erythrocyte receptors for parasite invasion are the most important. One of the red blood cell groups, the Duffy (Fy) antigen, recently renamed the Duffy antigen receptor for chemokines (DARC) because of its role in chemokine regulation, 5 is an indispensable receptor for P. vivax invasion of the erythrocyte.…”