scholarly journals Malaria vaccines: high-throughput tools for antigens discovery with potential for their development

2013 ◽  
pp. 121-128
Author(s):  
Nora Céspedes ◽  
Andrés Vallejo ◽  
Myriam Arévalo-Herrera ◽  
Sócrates Herrera
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Plasmodium Species ◽  
Cost Effective ◽  
Control Measures ◽  
Anopheles Mosquitoes ◽  
Malaria Vaccines ◽  
Large Numbers ◽  
Immune Potential ◽  
Selection Of

Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden worldwide. Plasmodium vivax is the second species of malaria worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatics tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.

scholarly journals Vaccines against malaria

2011 ◽  
Vol 366 (1579) ◽  
pp. 2806-2814 ◽  
Author(s):  
Adrian V. S. Hill
Keyword(s):  
Life Cycle ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Viral Vector ◽  
Cost Effective ◽  
Life Cycle Stage ◽  
Phase Iii ◽  
Small Scale ◽  
Vaccine Candidates ◽  
Adjuvant Vaccine

There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

scholarly journals Progress and Insights Toward an Effective Placental Malaria Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Benoît Gamain ◽  
Arnaud Chêne ◽  
Nicola K. Viebig ◽  
Nicaise Tuikue Ndam ◽  
Morten A. Nielsen
Keyword(s):  
Pregnant Women ◽  
Chondroitin Sulfate ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Placental Malaria ◽  
Premature Delivery ◽  
Phase I Clinical Trials ◽  
Malaria Vaccines ◽  
Clinical Consequences ◽  
Chondroitin Sulfate A

In areas where Plasmodium falciparum transmission is endemic, clinical immunity against malaria is progressively acquired during childhood and adults are usually protected against the severe clinical consequences of the disease. Nevertheless, pregnant women, notably during their first pregnancies, are susceptible to placental malaria and the associated serious clinical outcomes. Placental malaria is characterized by the massive accumulation of P. falciparum infected erythrocytes and monocytes in the placental intervillous spaces leading to maternal anaemia, hypertension, stillbirth and low birth weight due to premature delivery, and foetal growth retardation. Remarkably, the prevalence of placental malaria sharply decreases with successive pregnancies. This protection is associated with the development of antibodies directed towards the surface of P. falciparum-infected erythrocytes from placental origin. Placental sequestration is mediated by the interaction between VAR2CSA, a member of the P. falciparum erythrocyte membrane protein 1 family expressed on the infected erythrocytes surface, and the placental receptor chondroitin sulfate A. VAR2CSA stands today as the leading candidate for a placental malaria vaccine. We recently reported the safety and immunogenicity of two VAR2CSA-derived placental malaria vaccines (PRIMVAC and PAMVAC), spanning the chondroitin sulfate A-binding region of VAR2CSA, in both malaria-naïve and P. falciparum-exposed non-pregnant women in two distinct Phase I clinical trials (ClinicalTrials.gov, NCT02658253 and NCT02647489). This review discusses recent advances in placental malaria vaccine development, with a focus on the recent clinical data, and discusses the next clinical steps to undertake in order to better comprehend vaccine-induced immunity and accelerate vaccine development.

scholarly journals Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

2019 ◽  
Author(s):  
Jo-Anne Chan ◽  
David Wetzel ◽  
Linda Reiling ◽  
Kazutoyo Miura ◽  
Damien Drew ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Virus Like Particles ◽  
Malaria Vaccines ◽  
Membrane Feeding ◽  
B Virus ◽  
Vaccine Antigens ◽  
Novel Virus

ABSTRACTThe development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.

scholarly journals Down-selection of the VAR2CSA DBL1-2 expressed in E. coli as a lead antigen for placental malaria vaccine development

npj Vaccines ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Arnaud Chêne ◽  
Stéphane Gangnard ◽  
Célia Dechavanne ◽  
Sebastien Dechavanne ◽  
Anand Srivastava ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Placental Malaria ◽  
E Coli ◽  
Selection Of

An overview of aptamer: the prominent applications and different computational tools for its design

2020 ◽  
Vol 21 ◽  
Author(s):  
Mehrdad Ameri ◽  
Sedigheh Eskandari ◽  
Navid Nezafat
Keyword(s):  
Vaccine Development ◽  
3D Structure ◽  
Therapeutic Vaccine ◽  
Cost Effective ◽  
Computational Tools ◽  
High Affinity ◽  
Aptamer Selection ◽  
Effective Role ◽  
Systematic Evolution ◽  
Selection Of

Background: Aptamers are short single-stranded oligonucleotides; due to their 3D structure, they can specifically bind to various targets. They can target several molecules ranging from metal ions, organic components to proteins, and large cells. Methods: According to the high affinity of aptamers, they can be used for diagnosis, therapeutic, vaccine development, and gene silencing applications. The conventional method for aptamer selection is known as the systematic evolution of ligands by exponential (SELEX). However, despite the efficiency of SELEX as a screening procedure, it is beneficial to develop more rational procedures for aptamer selection. Results & Discussion: Herein, in silico approaches can play an effective role given their potential in representing an efficient, cost-effective, parallelizable, and rapid strategy. In recent years, several attempts have been applied to develop algorithms and software for the rational selection of aptamers. However, there is still a need for more efforts to achieve the most efficient techniques in this area. Conclusion: In this review, we aim to overview different computational approaches that are used for aptamer selection.

The Promise of a Malaria Vaccine—Are We Closer?

2018 ◽  
Vol 72 (1) ◽  
pp. 273-292 ◽  
Author(s):  
Matthew B. Laurens
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Phase 3 ◽  
Target Populations ◽  
The Past ◽  
Malaria Vaccines ◽  
Long Duration ◽  
Implementation Studies ◽  
Endemic Areas ◽  
Pilot Implementation

Malaria vaccine development has rapidly advanced in the past decade. The very first phase 3 clinical trial of the RTS,S vaccine was completed with over 15,000 African infants and children, and pilot implementation studies are underway. Next-generation candidate vaccines using novel antigens, platforms, or approaches targeting different and/or multiple stages of the Plasmodium life cycle are being tested. Many candidates, in various stages of development, promise enhanced efficacy of long duration and broad protection against genetically diverse malaria strains, with a few studies under way in target populations in endemic areas. Malaria vaccines together with other interventions promise interruption and eventual elimination of malaria in endemic areas.

scholarly journals Challenges and strategies for developing efficacious and long-lasting malaria vaccines

2019 ◽  
Vol 11 (474) ◽  
pp. eaau1458 ◽  
Author(s):  
James G. Beeson ◽  
Liriye Kurtovic ◽  
Carlota Dobaño ◽  
D. Herbert Opi ◽  
Jo-Anne Chan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Recent Progress ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Vaccine Effectiveness ◽  
Malaria Vaccines ◽  
Functional Immunity ◽  
Endemic Areas ◽  
New Strategies

Although there has been major recent progress in malaria vaccine development, substantial challenges remain for achieving highly efficacious and durable vaccines against Plasmodium falciparum and Plasmodium vivax malaria. Greater knowledge of mechanisms and key targets of immunity are needed to accomplish this goal, together with new strategies for generating potent, long-lasting, functional immunity against multiple antigens. Implementation considerations in endemic areas will ultimately affect vaccine effectiveness, so innovations to simplify and enhance delivery are also needed. Whereas challenges remain, recent exciting progress and emerging knowledge promise hope for the future of malaria vaccines.

scholarly journals New antigens for a multicomponent blood-stage malaria vaccine

2014 ◽  
Vol 6 (247) ◽  
pp. 247ra102-247ra102 ◽  
Author(s):  
Faith H. Osier ◽  
Margaret J. Mackinnon ◽  
Cécile Crosnier ◽  
Gregory Fegan ◽  
Gathoni Kamuyu ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Blood Stage ◽  
Transmission Season ◽  
Research Priority ◽  
Malaria Transmission Season ◽  
Development Pipeline ◽  
Blood Stage Malaria ◽  
Selection Of

An effective blood-stage vaccine against Plasmodium falciparum remains a research priority, but the number of antigens that have been translated into multicomponent vaccines for testing in clinical trials remains limited. Investigating the large number of potential targets found in the parasite proteome has been constrained by an inability to produce natively folded recombinant antigens for immunological studies. We overcame these constraints by generating a large library of biochemically active merozoite surface and secreted full-length ectodomain proteins. We then systematically examined the antibody reactivity against these proteins in a cohort of Kenyan children (n = 286) who were sampled at the start of a malaria transmission season and prospectively monitored for clinical episodes of malaria over the ensuing 6 months. We found that antibodies to previously untested or little-studied proteins had superior or equivalent potential protective efficacy to the handful of current leading malaria vaccine candidates. Moreover, cumulative responses to combinations comprising 5 of the 10 top-ranked antigens, including PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1, were associated with 100% protection against clinical episodes of malaria. These data suggest not only that there are many more potential antigen candidates for the malaria vaccine development pipeline but also that effective vaccination may be achieved by combining a selection of these antigens.

scholarly journals Design and assessment of TRAP-CSP fusion antigens as effective malaria vaccines

2019 ◽  
Author(s):  
Chafen Lu ◽  
Gaojie Song ◽  
Kristin Beale ◽  
Jiabin Yan ◽  
Emma Garst ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Repeat Region ◽  
Partial Protection ◽  
Adhesion Protein ◽  
Malaria Vaccines ◽  
Multi Stage ◽  
Antibody Titers

AbstractThe circumsporozoite protein (CSP) and thrombospondin-related adhesion protein (TRAP) are major targets for pre-erythrocytic malaria vaccine development. However, the most advanced CSP-based vaccine RTS,S provides only partial protection, highlighting the need for innovative approaches for vaccine design and development. Here we design and characterize TRAP-CSP fusion antigens, and evaluate their immunogenicity and protection against malaria infection. TRAP N-terminal folded domains were fused to CSP C-terminal fragments consisting of the C-terminal αTSR domain with or without the intervening repeat region. Homogenous, monomeric and properly folded fusion proteins were purified from mammalian transfectants. Notably, fusion improved expression of chimeras relative to the TRAP or CSP components alone. Immunization of BALB/c mice with the P. berghei TRAP-CSP fusion antigens formulated in AddaVax adjuvant elicited antigen-specific antibody responses. Remarkably, fusion antigens containing the CSP repeat region conferred complete sterile protection against P. berghei sporozoite challenge, and furthermore, mice that survived the challenge were completely protected from re-challenge 16 weeks after the first challenge. In contrast, fusion antigens lacking the CSP repeat region were less effective, indicating that the CSP repeat region provided enhanced protection, which correlated with higher antibody titers elicited by fusion antigens containing the CSP repeat region. In addition, we demonstrated that N-linked glycans had no significant effect on antibody elicitation or protection. Our results show that TRAP-CSP fusion antigens could be highly effective vaccine candidates. Our approach provides a platform for designing multi-antigen/multi-stage fusion antigens as next generation more effective malaria vaccines.

Medical Literature Searches -How Many Bibliographic Databases are Needed for Sufficient Retrieval in Medical Topics?

1985 ◽  
Vol 24 (03) ◽  
pp. 163-165 ◽  
Author(s):  
K. John
Keyword(s):  
Medical Literature ◽  
Cost Effective ◽  
Medical Faculty ◽  
Bibliographic Databases ◽  
Literature Searches ◽  
Selection Of

SummaryAs many bibliographic services in medicine are offered, literature searches in eight databases at DIMDI were performed to find out which database is most important in medicine. The distribution of publications from members of the medical faculty of Frankfurt University was examined. No save prediction is possible as to which database will yield most articles. Overlapping from different databases is often rather low. The selection of an appropriate database mix for sufficient recall and in a cost-effective manner.is a task for an experienced searcher.

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