Current Challenges in the Identification of Pre-Erythrocytic Malaria Vaccine Candidate Antigens

Plasmodium spp.-infected mosquitos inject sporozoites into the skin of a mammalian host during a blood meal. These enter the host's circulatory system and establish an infection in the liver. After a silent metamorphosis, merozoites invade the blood leading to the symptomatic and transmissible stages of malaria. The silent pre-erythrocytic malaria stage represents a bottleneck in the disease which is ideal to block progression to clinical malaria, through chemotherapeutic and immunoprophylactic interventions. RTS,S/AS01, the only malaria vaccine close to licensure, although with poor efficacy, blocks the sporozoite invasion mainly through the action of antibodies against the CSP protein, a major component of the pellicle of the sporozoite. Strikingly, sterile protection against malaria can be obtained through immunization with radiation-attenuated sporozoites, genetically attenuated sporozoites or through chemoprophylaxis with infectious sporozoites in animals and humans, but the deployability of sporozoite-based live vaccines pose tremendous challenges. The protection induced by sporozoites occurs in the pre-erythrocytic stages and is mediated mainly by antibodies against the sporozoite and CD8+ T cells against peptides presented by MHC class I molecules in infected hepatocytes. Thus, the identification of malaria antigens expressed in the sporozoite and liver-stage may provide new vaccine candidates to be included, alone or in combination, as recombinant protein-based, viru...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Source: IPS Inter Press Service - Health - Category: International Medicine & Public Health Authors: Tags: Global Headlines Health Humanitarian Emergencies TerraViva United Nations Women's Health Source Type: news
Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first vaccines against these pathogens were developed (1796 and 1800s). In contrast, Malaria, which is a protozoan-neglected disease, has been known since the 5th century BCE and, despite 2,500 years having passed since then, no human vaccine has yet been licensed for Malaria. Additionally, no modern human vaccine is currently licensed against Visceral or Cutaneous leishmaniasis. Vaccination against Malaria evolved from the inoculation of irradiated sporozoites through the bite of Anopheles mosquitoes in 1930's, whic...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The infection dynamics between different species of Plasmodium that infect the same human host can both suppress and exacerbate disease. This could arise from inter-parasite interactions, such as competition, from immune regulation, or both. The occurrence of protective, cross-species (heterologous) immunity is an unlikely event, especially considering that strain-transcending immunity within a species is only partial despite lifelong exposure to that species. Here we review the literature in humans and animal models to identify the contexts where heterologous immunity can arise, and which antigens may be involved. From th...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Lambraño J, Curtidor H, Avendaño C, Díaz-Arévalo D, Roa L, Vanegas M, Patarroyo ME, Patarroyo MA Abstract Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that ~219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. The disease cost the lives of more than 400,000 people, mainly in Africa. In spite of great efforts aimed at developing better prevention (i.e., a highly effective vaccine), diagnosis, and treatment methods for malaria, no efficient solution to this disease ...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
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Source: The Medical Futurist - Category: Information Technology Authors: Tags: Artificial Intelligence E-Patients Future of Medicine Future of Pharma Genomics Health Sensors & Trackers 3d printing AI bioprinting blockchain clinical trials CRISPR digital digital health drug development genetics Innovat Source Type: blogs
Authors: Szuster-Ciesielska A, Wawiórka L, Krokowski D, Grankowski N, Jarosz Ł, Lisiecka U, Tchórzewski M Abstract Malaria remains one the most infectious and destructive protozoan diseases worldwide. Plasmodium falciparum, a protozoan parasite with a complex life cycle and high genetic variability responsible for the difficulties in vaccine development, is implicated in most malaria-related deaths. In the course of study, we prepared a set of antigens based on P-proteins from P. falciparum and determined their immunogenicity in an in vivo assay on a mouse model. The pentameric complex P0-(P1-P2)2 wa...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
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Source: The Medical Futurist - Category: Information Technology Authors: Tags: Future of Medicine Africa AI artificial intelligence Congo digital digital health digital maps disease disease outbreak ebola epidemic Innovation technology Source Type: blogs
This study was carried out in accordance with the recommendations of Institutional Review Board of the Federal University of Bahia, Brazil, with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of the Federal University of Bahia, Brazil (approval number 693.111). Human Blood Samples and Preparation of Peripheral Blood Cells Peripheral blood mononuclear cells (PBMC) were separated from heparinized venous blood by Ficoll-Hypaque gradient centrifugation. Cells were then washed in ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Conclusions Toxoplasma gondii infection induces a strong innate and adaptive immune response. While the innate immunity is important for controlling the early stages of the infection (Yarovinsky, 2014), the adaptive immunity is critical for restricting the parasite replication during the later stages (Gazzinelli et al., 1992). Amongst the adaptive immune subsets, CD8 T cells are the primary effector cells while CD4 T cells play an essential helper role to maintain long-term immunity (Casciotti et al., 2002). Notwithstanding, a robust CD8 T cell immunity induced during acute phase of infection, does not result in the total...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
This study including human samples was carried out in accordance with the recommendations of the ICH/GCP guidelines, Comité de Etica para Investigación con Humanos, Centro Internacional de Vacunas (CECIV, Cali, Colombia), and the protocol approved by the CECIV. All subjects gave written informed consent in accordance with the Declaration of Helsinki. All animal protocols that include experimental animal procedures using mice and NHP were carried out in accordance with the US Animal Welfare Act and approved by the Emory University's Institutional Animal Care and Use Committee and followed accordingly....
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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