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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 -
Vaccine Dec 2015Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a... (Review)
Review
Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed.
Topics: Adjuvants, Immunologic; Animals; Antibodies, Protozoan; Clinical Trials as Topic; Drug Discovery; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Recombinant Proteins; Sporozoites; Vaccination; Vaccines, Subunit
PubMed: 26458807
DOI: 10.1016/j.vaccine.2015.09.093 -
Infection and Immunity Jan 2018Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or... (Review)
Review
Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration.
Topics: Animals; Antimalarials; Culicidae; Erythrocytes; Humans; Malaria; Malaria Vaccines; Plasmodium; Sporozoites
PubMed: 28923897
DOI: 10.1128/IAI.00479-17 -
Expert Review of Vaccines 2024
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Antibodies, Protozoan; Protozoan Proteins
PubMed: 38095048
DOI: 10.1080/14760584.2023.2292204 -
Vaccine Dec 2015Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands,... (Review)
Review
Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria.
Topics: Africa; Biomedical Research; Humans; Life Cycle Stages; Malaria Vaccines; Malaria, Vivax; Pacific Islands; Plasmodium vivax; South America
PubMed: 26428453
DOI: 10.1016/j.vaccine.2015.09.060 -
Vaccine Dec 2015Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of... (Review)
Review
Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of repetitive motifs and missing complementary signal(s) for optimal triggering of the immune response. Therefore, recombinant subunit vaccines require enhancement by vaccine delivery vehicles in order to attain adequate protective immunity. Particle-based delivery platforms, including particulate antigens and particulate adjuvants, are promising delivery vehicles for modifying the way in which immunogens are presented to both the innate and adaptive immune systems. These particle delivery platforms can also co-deliver non-specific immunostimodulators as additional adjuvants. This paper reviews efforts and advances of the Particle-based delivery platforms in development of vaccines against malaria, a disease that claims over 600,000 lives per year, most of them are children under 5 years of age in sub-Sahara Africa.
Topics: Adjuvants, Immunologic; Antigens, Protozoan; Humans; Malaria Vaccines; Nanoparticles; Vaccines, Subunit; Vaccines, Virus-Like Particle
PubMed: 26458803
DOI: 10.1016/j.vaccine.2015.09.097 -
Malaria Journal May 2017In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal.... (Review)
Review
In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.
Topics: Africa South of the Sahara; Malaria; Malaria Vaccines; Seasons; Vaccination; Vaccines, Synthetic
PubMed: 28464937
DOI: 10.1186/s12936-017-1841-9 -
Expert Review of Vaccines Feb 2021Transmission-blocking vaccines (TBV) prevent community spread of malaria by targeting mosquito sexual stage parasites, a life-cycle bottleneck, and will be used in... (Review)
Review
INTRODUCTION
Transmission-blocking vaccines (TBV) prevent community spread of malaria by targeting mosquito sexual stage parasites, a life-cycle bottleneck, and will be used in elimination programs. TBV rely on herd immunity to reduce mosquito infections and thereby new infections in both vaccine recipients and non-recipients, but do not provide protection once an individual receives an infectious mosquito bite which complicates clinical development.
AREAS COVERED
Here, we describe the concept and biology behind TBV, and we provide an update on clinical development of the leading vaccine candidate antigens. Search terms 'malaria vaccine,' 'sexual stages,' 'transmission blocking vaccine,' 'VIMT' and 'SSM-VIMT' were used for PubMed queries to identify relevant literature.
EXPERT OPINION
Candidates targeting zygote surface antigen Pfs25, and its orthologue Pvs25, induced functional activity in humans that reduced mosquito infection in surrogate assays, but require increased durability to be useful in the field. Candidates targeting gamete surface antigens Pfs230 and Pfs48/45, respectively, are in or nearing clinical trials. Nanoparticle platforms and adjuvants are being explored to enhance immunogenicity. Efficacy trials require special considerations, such as cluster-randomized designs to measure herd immunity that reduces human and mosquito infection rates, while addressing human and mosquito movements as confounding factors.
Topics: Animals; Antibodies, Protozoan; Antigens, Surface; Humans; Immunity, Herd; Malaria Vaccines; Malaria, Falciparum; Malaria, Vivax; Mosquito Control; Mosquito Vectors; Plasmodium falciparum; Plasmodium vivax
PubMed: 33478283
DOI: 10.1080/14760584.2021.1878028 -
Bundesgesundheitsblatt,... Jan 2020Globally, 3.1 billion people live in areas endemic for malaria (the tropics and subtropics). Annually, around 200 million fall ill, and around 500,000 persons die as... (Review)
Review
Globally, 3.1 billion people live in areas endemic for malaria (the tropics and subtropics). Annually, around 200 million fall ill, and around 500,000 persons die as a result of this infection. Mainly children are the victims. In order to control and eventually prevent any new infection, the development of effective vaccines is pivotal. In this review, background information about the history of vaccine development and malaria disease as well as possibilities for therapy and control is given. In the main part of the article, an update on the development of vaccines against Plasmodium falciparum is provided followed by an extensive discussion.Malaria is a parasitic infectious disease caused by the single cell organism Plasmodium. Five different Plasmodium species can induce disease in humans with P. falciparum being the origin for more than 99% of infections in Africa. The vector is the Anopheles mosquito. The life cycle of Plasmodium offers several approaches for vaccines to have an impact. Out of around 70 candidates, pre-erythrocytic vaccine candidates interfering with the liver phase of the parasite are the most developed. However, a vaccine with more than 75% efficacy, as required by the World Health Organization (WHO), is not yet in sight.Currently, for the first time, a moderately efficacious vaccine (RTS,S/AS01) is being applied in large-scale operations. But it is obvious that malaria can only be controlled in combination with concurring measures. For example, the use of impregnated mosquito nets, indoor residual spraying, elimination of vector breeding sites, rapid diagnosis, and therapy of the infection as well as a functioning health system are important elements, which can hardly be guaranteed in areas characterized by poverty.
Topics: Animals; Child; Germany; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 31828371
DOI: 10.1007/s00103-019-03070-1 -
Vaccine Dec 2015Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in... (Review)
Review
Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in significant morbidity and mortality worldwide. An effective malaria vaccine is considered by many to be the definitive solution. Yet, after decades of research, we are still without a vaccine that is capable of inducing robust, long lasting protection in naturally exposed individuals. Extensive sub-unit vaccine development focused on the blood stage of the malaria parasite has thus far yielded disappointing results. There is now a renewed focus on whole parasite vaccine strategies, particularly as they may overcome some of the inherent weaknesses deemed to be associated with the sub-unit approach. This review discusses the whole parasite vaccine strategy focusing on the blood stage of the malaria parasite, with an emphasis on recent advances and challenges in the development of killed and live attenuated vaccines.
Topics: Animals; Antigens, Protozoan; Humans; Life Cycle Stages; Malaria; Malaria Vaccines; Mice; Sporozoites; Vaccination; Vaccines, Attenuated
PubMed: 26428451
DOI: 10.1016/j.vaccine.2015.09.057