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https://www.readbyqxmd.com/read/28199305/sterile-protection-against-human-malaria-by-chemoattenuated-pfspz-vaccine
#1
Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J Campo, Meral Esen, Adam J Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R James, Peter F Billingsley, K C Natasha, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G Eappen, Tao Li, Richard E Stafford, Minglin Li, Phil L Felgner, Robert A Seder, Thomas L Richie, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites)...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28193898/systems-analysis-of-protective-immune-responses-to-rts-s-malaria-vaccination-in-humans
#2
Dmitri Kazmin, Helder I Nakaya, Eva K Lee, Matthew J Johnson, Robbert van der Most, Robert A van den Berg, W Ripley Ballou, Erik Jongert, Ulrike Wille-Reece, Christian Ockenhouse, Alan Aderem, Daniel E Zak, Jerald Sadoff, Jenny Hendriks, Jens Wrammert, Rafi Ahmed, Bali Pulendran
RTS,S is an advanced malaria vaccine candidate and confers significant protection against Plasmodium falciparum infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with Plasmodium-infected mosquitoes, 3 wk after the final immunization, resulted in ∼50% protection in both groups of vaccinees...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28187764/new-potential-plasmodium-brasilianum-hosts-tamarin-and-marmoset-monkeys-family-callitrichidae
#3
Denise A M Alvarenga, Anielle Pina-Costa, Cesare Bianco, Silvia B Moreira, Patricia Brasil, Alcides Pissinatti, Claudio T Daniel-Ribeiro, Cristiana F A Brito
BACKGROUND: Non-human primates (NHPs) as a source for Plasmodium infections in humans are a challenge for malaria elimination. In Brazil, two species of Plasmodium have been described infecting NHPs, Plasmodium brasilianum and Plasmodium simium. Both species are infective to man. Plasmodium brasilianum resembles morphologically, genetically and immunologically the human quartan Plasmodium malariae. Plasmodium brasilianum naturally infects species of non-human primates from all New World monkey families from a large geographic area...
February 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28182750/chemoprophylaxis-with-sporozoite-immunization-in-p-knowlesi-rhesus-monkeys-confers-protection-and-elicits-sporozoite-specific-memory-t-cells-in-the-liver
#4
Sathit Pichyangkul, Michele D Spring, Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Pattaraporn Vanachayangkul, Edmond J Remarque, Evelina Angov, Philip L Smith, David L Saunders
Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half...
2017: PloS One
https://www.readbyqxmd.com/read/28179404/a-plasmodium-vivax-plasmid-dna-and-adenovirus-vectored-malaria-vaccine-encoding-blood-stage-antigens-ama1-and-msp142-in-a-prime-boost-heterologous-immunization-regimen-partially-protects-aotus-monkeys-against-blood-stage-challenge
#5
Nicanor Obaldia, Michael G Stockelman, William Otero, Jennifer A Cockrill, Harini Ganeshan, Esteban N Abot, Jianfeng Zhang, Keith Limbach, Yupin Charoenvit, Denise L Doolan, De-Chu C Tang, Thomas L Richie
Malaria is caused by parasites of the genus Plasmodium that are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of P. falciparum it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside of Africa, stressing the importance of developing a vaccine against malaria. In this study we assess the immunogenicity and protective efficacy of two P. vivax antigens, AMA1 and MSP142 in a recombinant DNA plasmid prime/adenoviral vector (Ad) boost regimen in Aotus monkeys...
February 8, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28179403/evaluation-of-pvceltos-as-a-pre-erythrocytic-p-vivax-vaccine
#6
Eduardo Alves, Ahmed M Salman, Fabiana Leoratti, Cesar Lopez-Camacho, Martha Eva Viveros-Sandoval, Amar Lall, Aadil El-Turabi, Martin F Bachmann, Adrian V S Hill, Chris J Janse, Shahid M Khan, Arturo Reyes-Sandoval
Four different vaccine platforms each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (PvCelTOS) were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector ChAd63-PvCelTOS (Ad); a recombinant MVA-PvCelTOS (MVA); a bacteriophage Qβ-PvCelTOS virus-like particle (VLP); and recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c and outbred CD-1 mice were immunized using the following prime/boost regimens: Ad-MVA, Ad-VLP and Ad-protein...
February 8, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28176636/discovery-of-species-selective-and-resistance-breaking-anticholinesterase-insecticides-for-the-malaria-mosquito
#7
Paul R Carlier, Jeffrey R Bloomquist, Max Totrov, Jianyong Li
Great reductions in malaria mortality have been accomplished in the last 15 years, in part due to the widespread roll-out of insecticide-treated bednets across sub-Saharan Africa. To date, these nets only employ pyrethroids, insecticides that that target the voltage-gated sodium ion channel of the malaria vector, Anopheles gambiae. Due to the growing emergence of An. gambiae strains that are resistant to pyrethroids, there is an urgent need to develop new public health insecticides that engage a different target and possess extremely low mammalian toxicity...
February 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28174312/selective-whole-genome-amplification-is-a-robust-method-that-enables-scalable-whole-genome-sequencing-of-plasmodium-vivax-from-unprocessed-clinical-samples
#8
Annie N Cowell, Dorothy E Loy, Sesh A Sundararaman, Hugo Valdivia, Kathleen Fisch, Andres G Lescano, G Christian Baldeviano, Salomon Durand, Vince Gerbasi, Colin J Sutherland, Debbie Nolder, Joseph M Vinetz, Beatrice H Hahn, Elizabeth A Winzeler
: Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of Plasmodium vivax, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an ex vivo culture system...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#9
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
January 30, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28125584/the-real-mccoil-a-method-for-the-concurrent-estimation-of-the-complexity-of-infection-and-snp-allele-frequency-for-malaria-parasites
#10
Hsiao-Han Chang, Colin J Worby, Adoke Yeka, Joaniter Nankabirwa, Moses R Kamya, Sarah G Staedke, Grant Dorsey, Maxwell Murphy, Daniel E Neafsey, Anna E Jeffreys, Christina Hubbart, Kirk A Rockett, Roberto Amato, Dominic P Kwiatkowski, Caroline O Buckee, Bryan Greenhouse
As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28120745/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#11
Pramod N Nehete Bharti P Nehete Sriram Chitta Lawrence E Williams And Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model forhuman disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
January 24, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28115674/grammomys-surdaster-the-natural-host-for-plasmodium-berghei-parasites-as-a-model-to-study-whole-organism-vaccines-against-malaria
#12
Solomon Conteh, Charles Anderson, Lynn Lambert, Sachy Orr-Gonzalez, Jessica Herrod, Yvette L Robbins, Dariyen Carter, Stomy Bin Shamamba Karhemere, Pati Pyana, Philippe Büscher, Patrick E Duffy
Inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. To establish a more rigorous animal model, we acquired African woodland thicket rats of the genus Grammomys, the natural hosts for Plasmodium berghei Thicket rats were acquired and identified as Grammomys surdaster by skull and teeth measurements and mitochondrial DNA genotyping. Herein, we demonstrate that thicket rats are highly susceptible to infection by P berghei, and moderately susceptible to Plasmodium yoelii and Plasmodium chabaudi: 1-2 infected mosquito bites or 25-100 sporozoites administered by intravenous injection consistently resulted in patent parasitemia with P...
January 23, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28080988/medical-mycology-and-fungal-immunology-new-research-perspectives-addressing-a-major-world-health-challenge
#13
REVIEW
Neil A R Gow, Mihai G Netea
Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28077589/trimethoprim-sulfamethoxazole-prophylaxis-during-live-malaria-sporozoite-immunization-induces-long-lived-homologous-and-heterologous-protective-immunity-against-sporozoite-challenge
#14
Charlotte V Hobbs, Charles Anderson, Jillian Neal, Tejram Sahu, Solomon Conteh, Tatiana Voza, Jean Langhorne, William Borkowsky, Patrick E Duffy
Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28062360/determination-of-glutathione-redox-potential-and-ph-value-in-subcellular-compartments-of-malaria-parasites
#15
Franziska Mohring, Mahsa Rahbari, Bernd Zechmann, Stefan Rahlfs, Jude M Przyborski, Andreas J Meyer, Katja Becker
The malaria parasite Plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the Anopheles vector and its human host. In order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor roGFP2 coupled to human glutaredoxin 1 (roGFP2-hGrx1) as well as the ratiometric pH sensor pHluorin to the apicoplast and the mitochondrion of P. falciparum. Using live cell imaging, this allowed for the first time the determination of the pH values of the apicoplast (7...
January 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28053159/complete-attenuation-of-genetically-engineered-plasmodium-falciparum-sporozoites-in-human-subjects
#16
James G Kublin, Sebastian A Mikolajczak, Brandon K Sack, Matt E Fishbaugher, Annette Seilie, Lisa Shelton, Tracie VonGoedert, Melike Firat, Sara Magee, Emma Fritzen, Will Betz, Heather S Kain, Dorender A Dankwa, Ryan W J Steel, Ashley M Vaughan, D Noah Sather, Sean C Murphy, Stefan H I Kappe
Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52(-)/p36(-)/sap1(-)). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28049486/towards-eliminating-malaria-in-high-endemic-countries-the-roles-of-community-health-workers-and-related-cadres-and-their-challenges-in-integrated-community-case-management-for-malaria-a-systematic-review
#17
REVIEW
Bruno F Sunguya, Linda B Mlunde, Rakesh Ayer, Masamine Jimba
BACKGROUND: Human resource for health crisis has impaired global efforts against malaria in highly endemic countries. To address this, the World Health Organization (WHO) recommended scaling-up of community health workers (CHWs) and related cadres owing to their documented success in malaria and other disease prevention and management. Evidence is inconsistent on the roles and challenges they encounter in malaria interventions. This systematic review aims to summarize evidence on roles and challenges of CHWs and related cadres in integrated community case management for malaria (iCCM)...
January 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28038325/synthesis-biological-characterisation-and-structure-activity-relationships-of-aromatic-bisamidines-active-against-plasmodium-falciparum
#18
B Sauer, T S Skinner-Adams, A Bouchut, M J Chua, C Pierrot, F Erdmann, D Robaa, M Schmidt, J Khalife, K T Andrews, W Sippl
Malaria is one of the most significant tropical diseases and remains a major challenge due to the lack of a broadly effective vaccine and parasite resistance to current drugs. This means there is a need for new drug candidates with novel modes of action. Aromatic bisamidines, such as furamidine (DB75), were initially developed as anti-Trypanosoma agents however as clinical trials with furamidine highlighted potential side effects they were not pursued further in that setting. Despite apparent cytotoxicity liabilities the potency of furamidine against Plasmodium falciparum makes it a promising scaffold for the development of new anti-Plasmodium agents with improved selectivity...
December 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28031267/assessment-of-the-plasmodium-falciparum-pre-erythrocytic-antigen-uis3-as-a-potential-candidate-for-a-malaria-vaccine
#19
Rhea J Longley, Benedict R Halbroth, Ahmed M Salman, Katie J Ewer, Susanne H Hodgson, Chris J Janse, Shahid M Khan, Adrian V S Hill, Alexandra J Spencer
Efforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P...
December 28, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/28009103/experts-perceptions-on-china-s-capacity-to-manage-emerging-and-re-emerging-zoonotic-diseases-in-an-era-of-climate-change
#20
A Hansen, J Xiang, Q Liu, M X Tong, Y Sun, X Liu, K Chen, S Cameron, S Hanson-Easey, G-S Han, P Weinstein, C Williams, P Bi
Zoonotic diseases transmitted by arthropods and rodents are a major public health concern in China. However, interventions in recent decades have helped lower the incidence of several diseases despite the country's large, frequently mobile population and socio-economic challenges. Increasing globalization, rapid urbanization and a warming climate now add to the complexity of disease control and prevention and could challenge China's capacity to respond to threats of emerging and re-emerging zoonoses. To investigate this notion, face-to-face interviews were conducted with 30 infectious disease experts in four cities in China...
December 23, 2016: Zoonoses and Public Health
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