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Malaria Journal Nov 2020To maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1)...
To maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1) promote the development and short to medium term deployment of first generation vaccine candidates and (2) support innovation and discovery to identify and develop highly effective, long-lasting and affordable next generation malaria vaccines.
Topics: Biomedical Research; Drug Discovery; Malaria Vaccines
PubMed: 33228666
DOI: 10.1186/s12936-020-03491-3 -
Nature Communications Sep 2023Apical membrane antigen 1 (AMA1) is a key malaria vaccine candidate and target of neutralizing antibodies. AMA1 binds to a loop in rhoptry neck protein 2 (RON2L) to form...
Apical membrane antigen 1 (AMA1) is a key malaria vaccine candidate and target of neutralizing antibodies. AMA1 binds to a loop in rhoptry neck protein 2 (RON2L) to form the moving junction during parasite invasion of host cells, and this complex is conserved among apicomplexan parasites. AMA1-RON2L complex immunization achieves higher growth inhibitory activity than AMA1 alone and protects mice against Plasmodium yoelii challenge. Here, three single-component AMA1-RON2L immunogens were designed that retain the structure of the two-component AMA1-RON2L complex: one structure-based design (SBD1) and two insertion fusions. All immunogens elicited high antibody titers with potent growth inhibitory activity, yet these antibodies did not block RON2L binding to AMA1. The SBD1 immunogen induced significantly more potent strain-transcending neutralizing antibody responses against diverse strains of Plasmodium falciparum than AMA1 or AMA1-RON2L complex vaccination. This indicates that SBD1 directs neutralizing antibody responses to strain-transcending epitopes in AMA1 that are independent of RON2L binding. This work underscores the importance of neutralization mechanisms that are distinct from RON2 blockade. The stable single-component SBD1 immunogen elicits potent strain-transcending protection that may drive the development of next-generation vaccines for improved malaria and apicomplexan parasite control.
Topics: Animals; Mice; Malaria Vaccines; Antibodies, Neutralizing; Cell Membrane; Epitopes; Immunization
PubMed: 37660103
DOI: 10.1038/s41467-023-40878-7 -
Malaria Journal Jan 2024Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections... (Review)
Review
Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections and over 600,000 deaths across 85 countries. In the ongoing battle against malaria, a promising development has emerged with the endorsement by the World Health Organization (WHO) of the R21/Matrix-M Malaria Vaccine. Developed through a collaboration between the University of Oxford and Novavax, this vaccine has demonstrated remarkable efficacy, reaching 77% effectiveness in Phase 2 clinical trials. It is designed to be low-dose, cost-effective, and accessible, with approval for use in children under three years old. This perspective paper critically examines the R21/Matrix-M malaria vaccine, its development, potential impact on global malaria eradication efforts, and the challenges and opportunities it presents.
Topics: Child; Humans; Child, Preschool; Malaria Vaccines; Malaria
PubMed: 38216923
DOI: 10.1186/s12936-024-04846-w -
Vaccine Dec 2015Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated... (Review)
Review
Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated work by many researchers on different continents spanning more than half a century, a successful malaria vaccine remains elusive. Sequencing of the P. falciparum genome has revealed more than five thousand genes, providing the foundation for systematic approaches to discover candidate vaccine antigens. We are taking advantage of this wealth of information to discover new antigens that may be more effective vaccine targets. Herein, we describe different approaches to large-scale screening of the P. falciparum genome to identify targets of either antibody responses or T cell responses using human specimens collected in Controlled Human Malaria Infections (CHMI) or under conditions of natural exposure in the field. These genome, proteome and transcriptome based approaches offer enormous potential for the development of an efficacious malaria vaccine.
Topics: Antibodies, Protozoan; Antigens, Protozoan; Genome, Protozoan; Genomics; High-Throughput Screening Assays; Humans; Immunity, Innate; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Proteome; Transcriptome
PubMed: 26428458
DOI: 10.1016/j.vaccine.2015.09.059 -
Frontiers in Immunology 2022Pre-existing and intervening low-density infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and... (Review)
Review
Pre-existing and intervening low-density infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were often unrecognized since infrequent and often analytically insensitive parasitological testing was performed before and during trials. Molecular diagnostics now permits their detection, but investigators must weigh the cost, complexity, and personnel demands on the study and the laboratory when scheduling such tests. This paper discusses the effect of pre-existing and intervening, low-density infections on malaria vaccine trial endpoints and the current methods employed for their infection detection. We review detection techniques, that until recently, provided a dearth of cost-effective strategies for detecting low density infections. A recently deployed, field-tested, simple, and cost-effective molecular diagnostic strategy for detecting pre-existing and intervening infections from dried blood spots (DBS) in malaria-endemic settings is discussed to inform new clinical trial designs. Strategies that combine sensitive molecular diagnostic techniques with convenient DBS collections and cost-effective pooling strategies may enable more thorough and informative infection monitoring in upcoming malaria clinical trials and epidemiological studies.
Topics: Humans; Malaria; Malaria Vaccines; Molecular Diagnostic Techniques; Plasmodium falciparum
PubMed: 36203582
DOI: 10.3389/fimmu.2022.1003452 -
Parasitology International Feb 2021Vaccines against infectious diseases have had great successes in the history of public health. Major breakthroughs have occurred in the development of vaccine-based... (Review)
Review
Vaccines against infectious diseases have had great successes in the history of public health. Major breakthroughs have occurred in the development of vaccine-based interventions against viral and bacterial pathogens through the application of classical vaccine design strategies. In contrast the development of a malaria vaccine has been slow. Plasmodium falciparum malaria affects millions of people with nearly half of the world population at risk of infection. Decades of dedicated research has taught us that developing an effective vaccine will be time consuming, challenging, and expensive. Nevertheless, recent advancements such as the optimization of robust protein synthesis platforms, high-throughput immunoscreening approaches, reverse vaccinology, structural design of immunogens, lymphocyte repertoire sequencing, and the utilization of artificial intelligence, have renewed the prospects of an accelerated discovery of the key antigens in malaria. A deeper understanding of the major factors underlying the immunological and molecular mechanisms of malaria might provide a comprehensive approach to identifying novel and highly efficacious vaccines. In this review we discuss progress in novel antigen discoveries that leverage on the wheat germ cell-free protein synthesis system (WGCFS) to accelerate malaria vaccine development.
Topics: Antigens, Protozoan; Cell-Free System; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Protein Biosynthesis; Triticum
PubMed: 33137499
DOI: 10.1016/j.parint.2020.102224 -
Frontiers in Immunology 2018Each year malaria kills hundreds of thousands of people and infects hundreds of millions of people despite current control measures. An effective malaria vaccine will... (Review)
Review
Each year malaria kills hundreds of thousands of people and infects hundreds of millions of people despite current control measures. An effective malaria vaccine will likely be necessary to aid in malaria eradication. Vaccination using whole sporozoites provides an increased repertoire of immunogens compared to subunit vaccines across at least two life cycle stages of the parasite, the extracellular sporozoite, and intracellular liver stage. Three potential whole sporozoite vaccine approaches are under development and include genetically attenuated parasites, radiation attenuated sporozoites, and wild-type sporozoites administered in combination with chemoprophylaxis. Pre-clinical and clinical studies have demonstrated whole sporozoite vaccine immunogenicity, including humoral and cellular immunity and a range of vaccine efficacy that depends on the pre-exposure of vaccinated individuals. While whole sporozoite vaccines can provide protection against malaria in some cases, more recent studies in malaria-endemic regions demonstrate the need for improvements. Moreover, challenges remain in manufacturing large quantities of sporozoites for vaccine commercialization. A promising solution to the whole sporozoite manufacturing challenge is culturing methodology, which has been described for several species, including the major disease-causing human malaria parasite, . Here, we review whole sporozoite vaccine immunogenicity and culturing platforms for sporozoite production.
Topics: Humans; Immunogenicity, Vaccine; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Sporozoites
PubMed: 30619241
DOI: 10.3389/fimmu.2018.02748 -
Trends in Parasitology Nov 2020Malaria interventions may reduce the burden of clinical malaria disease, the transmission of malaria parasites, or both. As malaria interventions are developed and... (Review)
Review
Malaria interventions may reduce the burden of clinical malaria disease, the transmission of malaria parasites, or both. As malaria interventions are developed and evaluated, including those interventions primarily targeted at reducing disease, they may also impact parasite transmission. Achieving global malaria eradication will require optimizing the transmission-reducing potential of all available interventions. Herein, we discuss the relationship between malaria parasite transmission and disease, including mechanisms by which disease-targeting interventions might also impact parasite transmission. We then focus on three malaria interventions with strong evidence for reducing the burden of clinical malaria disease and examine their potential for also reducing malaria parasite transmission.
Topics: Animals; Antimalarials; Chemoprevention; Disease Eradication; Humans; Malaria; Malaria Vaccines; Plasmodium
PubMed: 32917511
DOI: 10.1016/j.pt.2020.07.013 -
Frontiers in Immunology 2019In the development of vaccines, the ability to initiate both innate and subsequent adaptive immune responses need to be considered. Live attenuated vaccines achieve this... (Review)
Review
In the development of vaccines, the ability to initiate both innate and subsequent adaptive immune responses need to be considered. Live attenuated vaccines achieve this naturally, while inactivated and sub-unit vaccines generally require additional help provided through delivery systems and/or adjuvants. Liposomes present an attractive adjuvant/delivery system for antigens. Here, we review the key aspects of immunity against parasites, liposome design considerations and their current application in the development of a malaria vaccine.
Topics: Animals; Humans; Liposomes; Malaria Vaccines; Plasmodium
PubMed: 30774635
DOI: 10.3389/fimmu.2019.00135 -
The Indian Journal of Medical Research Jun 2016Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens... (Review)
Review
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Culicidae; Humans; Immunity, Innate; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 27748294
DOI: 10.4103/0971-5916.191927