Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin

Aliprandini, Eduardo; Tavares, Joana; Panatieri, Raquel Hoffmann; Thiberge, Sabine; Yamamoto, Márcio; Silvie, Olivier; Ishino, Tomoko; Yuda, Masao; Dartevelle, Sylvie; Traincard, François; Boscardin, Sílvia Beatriz; Amino, Rogério

doi:10.1038/s41564-018-0254-z

Cited by 78 publications

(128 citation statements)

References 67 publications

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“…For all tests, 6-to 8-week-old females were used and allocated randomly to cages. Two independent immunization/blind challenge experiments were performed using 7 animals per experiment, as described previously [37].…”

Section: Parasites Mice and Mosquitoesmentioning

confidence: 99%

“…spzs, mosquitoes were fed on infected RjOrl:SWISS mice 1-2 days after emergence and kept in a humidified chamber at 21 • C. One week after infection, Pb/PvVK210-infected mosquitoes were fed on naïve RjOrl:SWISS mice. For footpad injections, Pb/PvVK210 spzs were collected from mosquito-infected salivary glands 21-28 days after the infectious blood meal [37].…”

Section: Parasites Mice and Mosquitoesmentioning

confidence: 99%

“…For this, 200,000 erythrocytes were examined for each sample. A quantitative analysis of protection was performed using the parasitemia log values on day 5 post-infection, when the blood parasites were still exponentially growing [37].…”

Section: Murine Sporozoite Challengementioning

confidence: 99%

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Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

et al. 2020

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Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP—All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria.

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Section: Parasites Mice and Mosquitoesmentioning

confidence: 99%

Section: Parasites Mice and Mosquitoesmentioning

confidence: 99%

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Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

et al. 2020

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“…CD8 + T cell‐mediated killing of the pathogen relied on G‐protein coupled receptor‐signaling, since treatment of antigen‐specific CD8 + T cells with pertussis toxin reduced both cluster formation around infected hepatocytes and pathogen death significantly . Recently, using propidium iodide staining in combination with fluorescence protein expression, Aliprandini et al demonstrated the cytotoxic effect of antibodies against the sporozoite form of P. yoelii . During cutaneous L. major infection, inhibition of the NO synthetase iNOS resulted in an increase of pathogen proliferation at the site of infection, suggesting that a chronic pressure on pathogen proliferation represents a sublethal mode of the control that is required for the eventual resolution of the infection .…”

Section: Effector Function Delivery and Impact On The Pathogenmentioning

confidence: 99%

From the Cradle to the Grave of an Infection: Host‐Pathogen Interaction Visualized by Intravital Microscopy

2019

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During infections, interactions between host immune cells and the pathogen occur in distinct anatomical locations and along defined time scales. This can best be assessed in the physiological context of an infection in the living tissue. Consequently, intravital imaging has enabled us to dissect the critical phases and events throughout an infection in real time in living tissues. Specifically, advances in visualizing specific cell types and individual pathogens permitted tracking the early events of tissue invasion of the pathogen, cellular interactions involved in the induction of the immune response as well the events implicated in clearance of the infection. In this respect, two vantage points have evolved since the initial employment of this technique in the field of infection biology. On the one hand, strategies acquired by the pathogen to establish within the host and circumvent or evade the immune defenses have been elucidated. On the other hand, analyzing infections from the immune system's perspective has led to insights into the dynamic cellular interactions that are involved in the initial recognition of the pathogen, immune induction as well as effector function delivery and immunopathology. Furthermore, an increasing interest in probing functional parameters in vivo has emerged, such as the analysis of pathogen reactivity to stress conditions imposed by the host organism in order to mediate clearance upon pathogen encounter. Here, we give an overview on recent intravital microscopy findings of hostpathogen interactions along the course of an infection, from both the immune system's and pathogen's perspectives. We also discuss recent developments and future perspectives in extracting intravital information beyond the localization of pathogens and their interaction with immune cells. Such reporter systems on the pathogen's physiological state and immune cell functions may prove useful in dissecting the functional dynamics of hostpathogen interactions.

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“…Though falling short of community-established goals, this promising first step validated the sporozoite as a vaccine target, with follow-up studies demonstrating that protection was mediated by antibodies targeting the sporozoite's major surface protein, the circumsporozoite protein (CSP) (12). Previous studies demonstrated that antibodies targeting CSP can immobilize sporozoites in vitro and in vivo and can exert a large proportion of their protective efficacy in the dermal inoculation site (2,(12)(13)(14). Though gliding motility is a good target for interventions, it has only been studied in the rodent malaria parasite, and only P. berghei has been subject to quantitative intravital imaging (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies

Hopp

Kanatani

Archer³

et al. 2019

Preprint

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Malaria infection starts with the injection of motile Plasmodium sporozoites into the host's skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functional in vivo assays with human malaria parasites are lacking. Here, we present the first characterization of P. falciparum sporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influences P. falciparum sporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier for Plasmodium. We observe that P. falciparum sporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targeting P. falciparum sporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoites in vivo. Screening of intervention strategies for in vivo efficacy against Pf sporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.

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Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin

Cited by 78 publications

References 67 publications

Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

From the Cradle to the Grave of an Infection: Host‐Pathogen Interaction Visualized by Intravital Microscopy

Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies

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