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Trends in Parasitology Jul 2019Malaria kills more than 600 000 people yearly, mainly children, and eradication is a global priority. Malaria transmission-blocking vaccines are advancing in clinical... (Review)
Review
Malaria kills more than 600 000 people yearly, mainly children, and eradication is a global priority. Malaria transmission-blocking vaccines are advancing in clinical trials, and strategies for their introduction must be prioritized among stakeholders and the vulnerable populations exposed to the disease.
Topics: Clinical Trials as Topic; Humans; Malaria; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins; Vulnerable Populations
PubMed: 31153722
DOI: 10.1016/j.pt.2019.04.008 -
Parasite Immunology Feb 2021Radiation-attenuated sporozoites induce sterilizing immunity and remain the 'gold standard' for malaria vaccine development. Despite practical challenges in translating... (Review)
Review
Radiation-attenuated sporozoites induce sterilizing immunity and remain the 'gold standard' for malaria vaccine development. Despite practical challenges in translating these whole sporozoite vaccines to large-scale intervention programmes, they have provided an excellent platform to dissect the immune responses to malaria pre-erythrocytic (PE) stages, comprising both sporozoites and exoerythrocytic forms. Investigations in rodent models have provided insights that led to the clinical translation of various vaccine candidates-including RTS,S/AS01, the most advanced candidate currently in a trial implementation programme in three African countries. With advances in immunology, transcriptomics and proteomics, and application of lessons from past failures, an effective, long-lasting and wide-scale malaria PE vaccine remains feasible. This review underscores the progress in PE vaccine development, focusing on our understanding of host-parasite immunological crosstalk in the tissue environments of the skin and the liver. We highlight possible gaps in the current knowledge of PE immunity that can impact future malaria vaccine development efforts.
Topics: Africa; Animals; Antibodies, Protozoan; Erythrocytes; Humans; Immunity; Immunity, Cellular; Life Cycle Stages; Liver; Malaria; Malaria Vaccines; Skin; Sporozoites
PubMed: 32981095
DOI: 10.1111/pim.12795 -
Expert Review of Vaccines Oct 2019: Highly effective malaria vaccines are essential component toward malaria elimination. Although the leading malaria vaccine, RTS,S/AS01, with modest efficacy is being... (Review)
Review
: Highly effective malaria vaccines are essential component toward malaria elimination. Although the leading malaria vaccine, RTS,S/AS01, with modest efficacy is being evaluated in a pilot feasibility trial, development of a malaria transmission-blocking vaccine (TBV) could make a major contribution toward malaria elimination. Only a few TBV antigens have reached pre-clinical or clinical development but with several challenges including difficulties in the expression of malaria recombinant proteins and low immunogenicity in humans. Therefore, novel approaches to accelerate TBV research to preclinical development are critical to generate an efficacious TBV.: PubMed was searched to review the progress and future prospects of malaria TBV research and development. We also reviewed registered trials at ClinicalTrials.gov as well as post-genome TBV candidate discovery research including our efforts.: Wheat germ cell-free protein synthesis technology can accelerate TBV development by overcoming some current challenges of TBV research.
Topics: Cell-Free System; Databases, Factual; Germ Cells; Humans; Immunogenicity, Vaccine; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins; Recombinant Proteins; Triticum
PubMed: 31566026
DOI: 10.1080/14760584.2019.1674145 -
Journal of Vector Borne Diseases 2023Leishmaniasis is a parasitic disease with different clinical forms caused by protozoan parasites of the genus Leishmania and transmitted by the bite of an infected... (Review)
Review
Leishmaniasis is a parasitic disease with different clinical forms caused by protozoan parasites of the genus Leishmania and transmitted by the bite of an infected female sandfly. According to the World Health Organization (WHO), it is the second most common parasitic disease after malaria and it is known that approximately 350 million people are at risk. The disease manifests itself in different clinical forms. In addition to asymptomatic cases, cutaneous leishmaniasis (CL), which creates large lesions on the skin, and visceral leishmaniasis (VL), which causes death if not treated, especially affecting the abdominal organs, are two important clinical forms. When the studies were examined, it was seen that a clinically used vaccine against any form of human leishmaniasis has not been developed yet. In some studies, it was stated that the lack of appropriate adjuvant was responsible for the failure to develop an effective Leishmania vaccine. We can say that strong adjuvants are needed to achieve successful vaccines. In this article, adjuvants and adjuvant candidates used in vaccine studies against leishmaniasis are discussed.
Topics: Female; Humans; Leishmaniasis Vaccines; Adjuvants, Immunologic; Leishmaniasis, Visceral; Leishmania; Leishmaniasis, Cutaneous
PubMed: 37417162
DOI: 10.4103/0972-9062.361179 -
Immunity Feb 2023The development of a transmission-blocking vaccine (TBV) against malaria is hampered by poor understanding of functional antibody responses. In this issue of Immunity,...
The development of a transmission-blocking vaccine (TBV) against malaria is hampered by poor understanding of functional antibody responses. In this issue of Immunity, Fabra-Garcia et al., Ivanochko et al., and Tang et al. isolate human monoclonal antibodies against the two most promising TBV candidates, Pfs48/45 and Pfs230, and map the epitopes responsible for potent transmission-reducing activity.
Topics: Humans; Malaria, Falciparum; Protozoan Proteins; Malaria Vaccines; Antibodies, Protozoan; Malaria; Plasmodium falciparum; Antigens, Protozoan
PubMed: 36792569
DOI: 10.1016/j.immuni.2023.01.018 -
Trends in Parasitology Jan 2022Last month, the World Health Organization (WHO) recommended widespread use of RTS,S/AS01 vaccine to prevent malaria in young African children, noting its 30% reduction...
Last month, the World Health Organization (WHO) recommended widespread use of RTS,S/AS01 vaccine to prevent malaria in young African children, noting its 30% reduction in deadly severe malaria. In a recent report, Das et al. describe antibody effector functions that may contribute to RTS,S efficacy and thereby guide vaccine improvements.
Topics: Child; Humans; Infant; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 34857495
DOI: 10.1016/j.pt.2021.11.006 -
Frontiers in Immunology 2019Parasites, including African trypanosomes, utilize several immune evasion strategies to ensure their survival and completion of their life cycles within their hosts. The... (Review)
Review
Parasites, including African trypanosomes, utilize several immune evasion strategies to ensure their survival and completion of their life cycles within their hosts. The defense factors activated by the host to resolve inflammation and restore homeostasis during active infection could be exploited and/or manipulated by the parasites in an attempt to ensure their survival and propagation. This often results in the parasites evading the host immune responses as well as the host sustaining some self-inflicted collateral tissue damage. During infection with African trypanosomes, both effector and suppressor cells are activated and the balance between these opposing arms of immunity determines susceptibility or resistance of infected host to the parasites. Immune evasion by the parasites could be directly related to parasite factors, (e.g., antigenic variation), or indirectly through the induction of suppressor cells following infection. Several cell types, including suppressive macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells have been shown to contribute to immunosuppression in African trypanosomiasis. In this review, we discuss the key factors that contribute to immunity and immunosuppression during infection, and how these factors could aid immune evasion by African trypanosomes. Understanding the regulatory mechanisms that influence resistance and/or susceptibility during African trypanosomiasis could be beneficial in designing effective vaccination and therapeutic strategies against the disease.
Topics: Animals; Humans; Immune Evasion; Macrophages; Myeloid-Derived Suppressor Cells; Protozoan Vaccines; T-Lymphocytes, Regulatory; Trypanosoma congolense; Trypanosomiasis, African
PubMed: 31824512
DOI: 10.3389/fimmu.2019.02738 -
Biochimica Et Biophysica Acta.... May 2020Chagas disease is currently endemic to 21 Latin-American countries and has also become a global concern because of globalization and mass migration of chronically... (Review)
Review
Chagas disease is currently endemic to 21 Latin-American countries and has also become a global concern because of globalization and mass migration of chronically infected individuals. Prophylactic and therapeutic vaccination might contribute to control the infection and the pathology, as complement of other strategies such as vector control and chemotherapy. Ideal prophylactic vaccine would produce sterilizing immunity; however, a reduction of the parasite burden would prevent progression from Trypanosoma cruzi infection to Chagas disease. A therapeutic vaccine for Chagas disease may improve or even replace the treatment with current drugs which have several side effects and require long term treatment that frequently leads to therapeutic withdrawal. Here, we will review some aspects about sub-unit vaccines, the rationale behind the selection of the immunogen, the role of adjuvants, the advantages and limitations of DNA-based vaccines and the idea of therapeutic vaccines. One of the main limitations to advance vaccine development against Chagas disease is the high number of variables that must be considered and the lack of uniform criteria among research laboratories. To make possible comparisons, much of this review will be focused on experiments that kept many variables constant including antigen mass/doses, type of eukaryotic plasmid, DNA-delivery system, mice strain and sex, lethal and sublethal model of infection, and similar immunogenicity and efficacy assessments.
Topics: Animals; Antigens, Protozoan; Chagas Cardiomyopathy; Disease Models, Animal; Female; Humans; Immunogenicity, Vaccine; Male; Mice; Protozoan Vaccines; Research Design; Sex Factors; Trypanosoma cruzi; Vaccines, Subunit
PubMed: 31904415
DOI: 10.1016/j.bbadis.2019.165658 -
Trends in Parasitology Feb 2020Each year over 200 million malaria infections occur, with over 400 000 associated deaths. Vaccines formed with attenuated whole parasites can induce protective memory... (Review)
Review
Each year over 200 million malaria infections occur, with over 400 000 associated deaths. Vaccines formed with attenuated whole parasites can induce protective memory CD8 T cell responses against liver-stage malaria; however, widespread administration of such vaccines is logistically challenging. Recent scientific findings are delineating how protective memory CD8 T cell populations are primed and maintained and how such cells mediate immunity to liver-stage malaria. Memory CD8 T cell anatomic localization and expression of transcription factors, homing receptors, and signaling molecules appear to play integral roles in protective immunity to liver-stage malaria. Further investigation of how such factors contribute to optimal protective memory CD8 T cell generation and maintenance in humans will inform efforts for improved vaccines.
Topics: Antigens, Protozoan; CD8-Positive T-Lymphocytes; Immunologic Memory; Liver; Malaria; Malaria Vaccines
PubMed: 31843536
DOI: 10.1016/j.pt.2019.11.004 -
Acta Tropica Dec 2019Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute... (Review)
Review
Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute infection and chronic disease. Studies in experimental models have suggested that the protective immunity against T. cruzi infection requires the elicitation of Th1 cytokines, lytic antibodies and the concerted activities of macrophages, T helper cells, and cytotoxic T lymphocytes (CTLs). In this review, we summarize the research efforts in vaccine development to date and the challenges faced in achieving an efficient prophylactic or therapeutic vaccine against human CD.
Topics: Animals; Chagas Disease; Humans; Protozoan Vaccines; Trypanosoma cruzi
PubMed: 31513763
DOI: 10.1016/j.actatropica.2019.105168