Malaria Vaccines: Recent Advances and New Horizons

Draper, Simon J.; Sack, Brandon K.; King, C. Richter; Nielsen, Carolyn M.; Rayner, Julian C.; Higgins, Matthew K.; Long, Carole A.; Seder, Robert A.

doi:10.1016/j.chom.2018.06.008

Cited by 262 publications

(265 citation statements)

References 120 publications

(132 reference statements)

Supporting

Mentioning

249

Contrasting

Unclassified

Order By: Relevance

“…[28] Suitable therapeutic targets and vaccine development are under intense investigations. [29] Thus, our findings and approach may facilitate future breakthroughs in the treatment of malaria, a field that has perplexed researchers for centuries.…”

Section: Resultsmentioning

confidence: 92%

Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase

Pramanik

Thaker

Perumal

et al. 2020

Molecular Informatics

View full text Add to dashboard Cite

Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in > 1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the~5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis -i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.

show abstract

Section: Resultsmentioning

confidence: 92%

Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase

Pramanik

Thaker

Perumal

et al. 2020

Molecular Informatics

View full text Add to dashboard Cite

show abstract

“…Humanized mouse models and engineered livers are being developed to support P. vivax parasites and improve our knowledge of immunity to this Plasmodial species . To date, there have been more than 200 human trials to test malaria vaccine candidates and only one has shown enough protective efficacy to advance to Phase 3 trials . Malaria vaccine strategies strive to do better than naturally acquired immunity by improving durability and increasing the breadth of the immune repertoire, which epidemiologic studies have shown decreases the severity and frequency of infections even though it does not confer lifelong sterilizing immunity.…”

Section: Overview Of Malariamentioning

confidence: 99%

“…The generation of protective, long‐lasting antibodies is the ultimate goal of vaccine‐induced immunity to malaria . However, determining which P. falciparum antigens and what immune signals are key to achieving this goal have been hindered by several factors.…”

Section: Antibody‐mediated Immunity and Cd4 T‐cell Helpmentioning

confidence: 99%

“…The generation of protective, long-lasting antibodies is the ultimate goal of vaccine-induced immunity to malaria. 5 However, determining which P. falciparum antigens and what immune signals are key to achieving this goal have been hindered by several factors. The first is prioritizing candidate antigens and then imputing the impact of antigenic variation and antigenic polymorphisms on sustainable immune protection.…”

Section: Antibody-mediated Immunit Y and CD T-cell Helpmentioning

confidence: 99%

See 1 more Smart Citation

Immune effector mechanisms in malaria: An update focusing on human immunity

Moormann

Nixon

Forconi

2019

Parasite Immunology

View full text Add to dashboard Cite

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.

show abstract

“…Vaccines have been successful in dramatically lowering infection rates for diseases like measles, mumps, rubella, diphtheria, pertussis and many more, and have led to the complete eradication of smallpox and near-eradication of polio [1][2][3][4]. However, safe and effective vaccines for some of the most prevalent and crippling diseases known to mankind remain elusive, despite decades of research [5][6][7]. Against a backdrop of a rise in vaccine hesitancy across the world, the development of effective drug treatments for patients suffering from infectious diseases is imperative [8].…”

Section: Introductionmentioning

confidence: 99%

Viral replicons as valuable tools for drug discovery

Hannemann¹

2020

Drug Discovery Today

View full text Add to dashboard Cite

RNA viruses can cause severe diseases such as dengue, Lassa, chikungunya and Ebola. Many of these viruses can only be propagated under high containment levels, necessitating the development of low containment surrogate systems such as subgenomic replicons and minigenome systems. Replicons are self-amplifying recombinant RNA molecules expressing proteins sufficient for their own replication but which do not produce infectious virions. Replicons can persist in cells and are passed on during cell division, enabling quick, efficient and high-throughput testing of drug candidates that act on viral transcription, translation and replication. This review will explore the history and potential for drug discovery of hepatitis C virus, dengue virus, respiratory syncytial virus, Ebola virus and norovirus replicon and minigenome systems.

show abstract

Malaria Vaccines: Recent Advances and New Horizons

Cited by 262 publications

References 120 publications

Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase

Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase

Immune effector mechanisms in malaria: An update focusing on human immunity

Viral replicons as valuable tools for drug discovery

Contact Info

Product

Resources

About