Gliding Motility of Babesia bovis Merozoites Visualized by Time-Lapse Video Microscopy

BACKGROUND: Babesia bovis is an apicomplexan intraerythrocytic protozoan parasite that induces babesiosis in cattle after transmission by ticks. During specific stages of the apicomplexan parasite lifecycle, such as the sporozoites of Plasmodium falciparum and tachyzoites of Toxoplasma gondii, host cells are targeted for invasion using a unique, active process termed "gliding motility". However, it is not thoroughly understood how the merozoites of B. bovis target and invade host red blood cells (RBCs), and gliding motility has so far not been observed in the parasite. METHODOLOGY/PRINCIPAL FINDINGS: Gliding motility of B. bovis merozoites was revealed by time-lapse video microscopy. The recorded images revealed that the process included egress of the merozoites from the infected RBC, gliding motility, and subsequent invasion into new RBCs. The gliding motility of B. bovis merozoites was similar to the helical gliding of Toxoplasma tachyzoites. The trails left by the merozoites were detected by indirect immunofluorescence assay using antiserum against B. bovis merozoite surface antigen 1. Inhibition of gliding motility by actin filament polymerization or depolymerization indicated that the gliding motility was driven by actomyosin dependent process. In addition, we revealed the timing of breakdown of the parasitophorous vacuole. Time-lapse image analysis of membrane-stained bovine RBCs showed formation and breakdown of the parasitophorous vacuole within ten minutes of invasion. CONCLUSIONS/SIGNIFICANCE: This is the first report of the gliding motility of B. bovis. Since merozoites of Plasmodium parasites do not glide on a substrate, the gliding motility of B. bovis merozoites is a notable finding

Immunological mechanisms underlying protection mediated by RTS,S: a review of the available data

The RTS,S/AS candidate malaria vaccine has demonstrated efficacy against a variety of endpoints in Phase IIa and Phase IIb trials over more than a decade. A multi-country phase III trial of RTS,S/AS01 is now underway with submission as early as 2012, if vaccine safety and efficacy are confirmed. The immunologic basis for how the vaccine protects against both infection and disease remains uncertain. It is, therefore, timely to review the information currently available about the vaccine with regard to how it impacts the human-Plasmodium falciparum host-pathogen relationship. In this article, what is known about mechanisms involved in partial protection against malaria induced by RTS,S is reviewed

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Vaccine adjuvants CpG (oligodeoxynucleotides ODNs), MPL (3-O-deacylated monophosphoryl lipid A) and naloxone-enhanced Th1 immune response to the Plasmodium vivax recombinant thrombospondin-related adhesive protein (TRAP) in mice

Despite considerable efforts toward vaccine development over decades, there is no available effective vaccine against Plasmodium vivax. Thrombospondin-related adhesive protein of P. vivax (PvTRAP) is essential for sporozoite motility and invasions into mosquito’s salivary gland and vertebrate’s hepatocyte; hence, it is a promising target for pre-erythrocytic vaccine. In the current investigation, the role of antibodies and cellular immune responses induced by purified recombinant PvTRAP (rPvTRAP) delivered in three adjuvants, naloxone (NLX), CpG oligodeoxynucleotides ODN1826 (CpG-ODN), and 3-O-deacylated monophosphoryl lipid A (MPL), alone and in combination was evaluated in immunized C57BL/6 mice. The highest level and the avidity of anti-PvTRAP IgG (mean OD490nm 2.55), IgG2b (mean OD490nm 1.68), and IgG2c (mean OD490nm 1.466) were identified in the group received rPvTRA/NLX–MPL–CpG. This group also presented the highest IgG2c/IgG1 (2.58) and IgG2b/IgG1 (2.95) ratio when compared to all other groups, and among the adjuvant groups, the lowest IgG2c/IgG1 (1.86) and IgG2b/IgG1 (2.25) ratio was observed in mice receiving rPvTRAP/NLX. Mice receiving rPvTRAP/adjuvants induced significantly the higher levels of interferon gamma (IFN-γ), low level of detectable IL-10, and no detectable IL-4 production. The present result revealed that PvTRAP is immunogenic and its administration with CPG, MPL, and NLX in C57BL/6 mice induced Th1 immune response. Besides, the rPvTRAP delivery in the mixed formulation of those adjuvants had more potential to increase the level, avidity, and persistence of anti-TRAP antibodies. However, it warrants further assessment to test the blocking activity of the produced antibodies in immunized mice with different adjuvant formulations