Genetically attenuated parasite vaccines induce contact-dependent CD8+ T cell killing of Plasmodium yoelii liver stage-infected hepatocytes.

The production of IFN-gamma by CD8(+) T cells is an important hallmark of protective immunity induced by irradiation-attenuated sporozoites against malaria. Here, we demonstrate that protracted sterile protection conferred by a Plasmodium yoelii genetically attenuated parasite (PyGAP) vaccine was completely dependent on CD8(+) T lymphocytes but only partially dependent on IFN-gamma. We used live cell imaging to document that CD8(+) CTL from PyGAP-immunized mice directly killed hepatocyte infected with a liver stage parasite.

Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick.

Tick saliva contains potent antihemostatic molecules that help ticks obtain their enormous blood meal during prolonged feeding. We isolated thrombin inhibitors present in the salivary gland extract from partially fed female Amblyomma variegatum, the tropical bont tick, and characterized the most potent, variegin, one of the smallest (32 residues) thrombin inhibitors found in nature. Full-length variegin and two truncated variants were chemically synthesized.

Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria.

In Plasmodium falciparum, var genes encode adhesive proteins that are transported to the surface of infected erythrocytes and act as major virulence determinants for infected erythrocyte binding and immune evasion. Var genes are highly diverse and can be classified into five major groups (UpsA, B, C, D, and E). Previous serological studies have suggested that the UpsA var group may contain common antigenic types that have important roles in severe childhood malaria.

An antivector vaccine protects against a lethal vector-borne pathogen.

Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP) of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV) transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks.

A cross-reactive tick cement antigen is a candidate broad-spectrum tick vaccine.

Truncated constructs of 64P (64TRPs), a secreted cement protein from salivary glands of the tick Rhipicephalus appendiculatus, provided cross-protection against Rhipicephalus sanguineus and Ixodes ricinus, apparently by targeting antigens in the midgut and salivary glands of adults and nymphs, causing mortality. Tick feeding on 64TRP-immunised animals stimulated local inflammatory immune responses (involving basophils, eosinophils, lymphocytes, mast cells, macrophages and dendritic-like cells) that boosted the immune status of vaccinated animals. The vaccine trial results, and antigenic cross-reactivity of 64TRPs with R.

Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites.

Malaria in pregnancy is a serious complication associated with parasitized erythrocyte (PE) sequestration in the placenta. Recent work suggests that var genes could play an important role in PE binding to chondroitin sulfate A (CSA), a primary placental adherence receptor. Here, we confirm that var2CSA is transcriptionally up-regulated in CSA-binding parasites and define CSA-binding domains in var2CSA.

Dual action ectoparasite vaccine targeting 'exposed' and 'concealed' antigens.

Blood-feeding ectoparasites, such as mosquitoes, sandflies and ticks, transmit many disease agents. Their control relies on large-scale, repeated use of chemical pesticides. An alternative, targeted and environmentally friendly approach is to develop anti-ectoparasite vaccines.