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https://www.readbyqxmd.com/read/28108531/plasmodium-sporozoite-biology
#1
Friedrich Frischknecht, Kai Matuschewski
Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies...
January 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28098083/vaccination-against-malaria-a-dream-too-distant
#2
Mohammad Ali, Vivek Arya
No abstract text is available yet for this article.
September 2016: National Medical Journal of India
https://www.readbyqxmd.com/read/28097230/protection-against-plasmodium-falciparum-malaria-by-pfspz-vaccine
#3
Judith E Epstein, Kristopher M Paolino, Thomas L Richie, Martha Sedegah, Alexandra Singer, Adam J Ruben, Sumana Chakravarty, April Stafford, Richard C Ruck, Abraham G Eappen, Tao Li, Peter F Billingsley, Anita Manoj, Joana C Silva, Kara Moser, Robin Nielsen, Donna Tosh, Susan Cicatelli, Harini Ganeshan, Jessica Case, Debbie Padilla, Silas Davidson, Lindsey Garver, Elizabeth Saverino, Tooba Murshedkar, Anusha Gunasekera, Patrick S Twomey, Sharina Reyes, James E Moon, Eric R James, Natasha Kc, Minglin Li, Esteban Abot, Arnel Belmonte, Kevin Hauns, Maria Belmonte, Jun Huang, Carlos Vasquez, Shon Remich, Mary Carrington, Yonas Abebe, Amy Tillman, Bradley Hickey, Jason Regules, Eileen Villasante, B Kim Lee Sim, Stephen L Hoffman
BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28097063/interferon-%C3%AE-responses-to-plasmodium-falciparum-vaccine-candidate-antigens-decrease-in-the-absence-of-malaria-transmission
#4
Cyrus Ayieko, Bilha S Ogola, Lyticia Ochola, Gideon A M Ngwena, George Ayodo, James S Hodges, Gregory S Noland, Chandy C John
BACKGROUND: Malaria elimination campaigns are planned or active in many countries. The effects of malaria elimination on immune responses such as antigen-specific IFN- γ responses are not well characterized. METHODS: IFN- γ responses to the P. falciparum antigens circumsporozoite protein, liver stage antigen-1, thrombospondin-related adhesive protein, apical membrane antigen-1, MB2, and merozoite surface protein-1 were tested by ELISA in 243 individuals in highland Kenya in April 2008, October 2008, and April 2009, after a one-year period of interrupted malaria transmission from April 2007 to March 2008...
2017: PeerJ
https://www.readbyqxmd.com/read/28096331/one-step-design-of-a-stable-variant-of-the-malaria-invasion-protein-rh5-for-use-as-a-vaccine-immunogen
#5
Ivan Campeotto, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M Marshall, Sarah E Silk, Katherine E Wright, Simon J Draper, Matthew K Higgins, Sarel J Fleishman
Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093536/noma-overview-of-a-neglected-disease-and-human-rights-violation
#6
REVIEW
M Leila Srour, Klaas Marck, Denise Baratti-Mayer
Noma is an orofacial gangrene affecting malnourished children and mainly observed in tropical countries, particularly sub-Saharan Africa. Epidemiological data on noma are scarce, but a current estimate of the global incidence is 30,000-40,000 cases per year, with a mortality rate of approximately 85% and a burden of disease calculated to be a loss of 1-10 million disability-adjusted life years. The etiology of noma is multifactorial with malnutrition as an ever present factor, often in combination with concomitant diseases, such as measles, malaria, and human immunodeficiency virus (HIV), and poor oral hygiene...
January 16, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28091576/adjuvant-and-carrier-protein-dependent-t-cell-priming-promotes-a-robust-antibody-response-against-the-plasmodium-falciparum-pfs25-vaccine-candidate
#7
Andrea J Radtke, Charles F Anderson, Nicolas Riteau, Kelly Rausch, Puthupparampil Scaria, Emily R Kelnhofer, Randall F Howard, Alan Sher, Ronald N Germain, Patrick Duffy
Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089547/antibody-profiles-to-wheat-germ-cell-free-system-synthesized-plasmodium-falciparum-proteins-correlate-with-protection-from-symptomatic-malaria-in-uganda
#8
Bernard N Kanoi, Eizo Takashima, Masayuki Morita, Michael T White, Nirianne M Q Palacpac, Edward H Ntege, Betty Balikagala, Adoke Yeka, Thomas G Egwang, Toshihiro Horii, Takafumi Tsuboi
The key targets of protective antibodies against Plasmodium falciparum remain largely unknown. In this study, we determined immunoreactivity to 1827 recombinant proteins derived from 1565 genes representing ∼30% of the entire P. falciparum genome, for identification of novel malaria vaccine candidates. The recombinant proteins were expressed by wheat germ cell-free system, a platform that can synthesize quality plasmodial proteins that elicit biologically active antibodies in animals. Sera were obtained from indigenous residents of a malaria endemic region in Northern Uganda who were enrolled at the start of a rainy season and prospectively monitored for symptomatic malaria episodes for a year...
January 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28087668/the-threshold-of-protection-from-liver-stage-malaria-relies-on-a-fine-balance-between-the-number-of-infected-hepatocytes-and-effector-cd8-t-cells-present-in-the-liver
#9
Alexandra J Spencer, Rhea J Longley, Anita Gola, Marta Ulaszewska, Teresa Lambe, Adrian V S Hill
Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8(+) T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8(+) T cell response in the liver following Plasmodium berghei sporozoite challenge...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087198/cloning-characterization-and-transmission-blocking-potential-of-midgut-carboxypeptidase-a-in-anopheles-stephensi
#10
V VenkatRao, Surendra K Kumar, P Sridevi, Vijaykumar Yogesh Muley, R K Chaitanya
Transmission-blocking vaccines (TBV) interrupt malaria parasite transmission and hence form an important component for malaria eradication. Mosquito midgut exopeptidases such as aminopeptidase N & carboxypeptidase B have demonstrated TBV potential. In the present study, we cloned and characterized carboxypeptidase A (CPA) from the midgut of an important malarial vector, Anopheles stephensi. ClustalW amino acid alignment and in silico 3-dimensional structure analysis of CPA predicted the presence of active sites involved in zinc and substrate binding that are conserved among all the known mosquito species...
January 10, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28081253/probability-of-transmission-of-malaria-from-mosquito-to-human-is-regulated-by-mosquito-parasite-density-in-na%C3%A3-ve-and-vaccinated-hosts
#11
Thomas S Churcher, Robert E Sinden, Nick J Edwards, Ian D Poulton, Thomas W Rampling, Patrick M Brock, Jamie T Griffin, Leanna M Upton, Sara E Zakutansky, Katarzyna A Sala, Fiona Angrisano, Adrian V S Hill, Andrew M Blagborough
Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28081133/the-power-of-malaria-vaccine-trials-using-controlled-human-malaria-infection
#12
Luc E Coffeng, Cornelus C Hermsen, Robert W Sauerwein, Sake J de Vlas
Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals...
January 2017: PLoS Computational Biology
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/28077251/theoretical-implications-of-a-pre-erythrocytic-plasmodium-vivax-vaccine-for-preventing-relapses
#14
Michael White, Rogerio Amino, Ivo Mueller
Preventing malaria infection through vaccination requires preventing every sporozoite inoculated by mosquito bite: a major challenge for Plasmodium falciparum. Plasmodium vivax sporozoites consist of tachysporozoites causing primary infection and bradysporozoites leading to relapses. We hypothesise that a candidate P. vivax vaccine with low efficacy against primary infection may substantially reduce transmission by preventing relapses.
January 8, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28075558/immunological-principles-guiding-the-rational-design-of-particles-for-vaccine-delivery
#15
Katelyn T Gause, Adam K Wheatley, Jiwei Cui, Yan Yan, Stephen J Kent, Frank Caruso
Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28069075/domestic-trends-in-malaria-research-and-development-in-china-and-its-global-influence
#16
Yang-Mu Huang, Lu-Wen Shi, Rui She, Jing Bai, Shi-Yong Jiao, Yan Guo
BACKGROUND: Though many countries, including China, are moving towards malaria elimination, malaria remains a major global health threat. Due to the spread of antimalarial drug resistance and the need for innovative medical products during the elimination phase, further research and development (R&D) of innovative tools in both epidemic and elimination areas is needed. This study aims to identify the trends and gaps in malaria R&D in China, and aims to offer suggestions on how China can be more effectively involved in global malaria R&D...
January 10, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28065475/could-the-rts-s-as01-meningitis-safety-signal-really-be-a-protective-effect-of-rabies-vaccine
#17
REVIEW
Bradford D Gessner, Darryn L Knobel, Anne Conan, Adam Finn
The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5-17month but not the 6-12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5-17month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28059665/efficacy-of-phase-3-trial-of-rts-s-as01-malaria-vaccine-in-infants-a-systematic-review-and-meta-analysis
#18
Shima Mahmoudi, Hossein Keshavarz
Although vaccines would be the ideal tool for control, prevention, elimination, and eradication of many infectious diseases, developing of parasites vaccines such as malaria vaccine is very complex. The most advanced malaria vaccine candidate is RTS,S, a pre-erythrocytic vaccine for which pivotal phase III trial design is underway. Few recent malaria vaccine review articles have attempted to outline of all clinical trials that have occurred globally and no meta-analysis was performed on efficacy of Phase 3 Trial of RTS, S/AS01 Malaria vaccine up to now in infants...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28057055/functional-characterization-of-plasmodium-berghei-psop25-during-ookinete-development-and-as-a-malaria-transmission-blocking-vaccine-candidate
#19
Wenqi Zheng, Fei Liu, Yiwen He, Qingyang Liu, Gregory B Humphreys, Takafumi Tsuboi, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P...
January 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28056035/a-systematic-review-of-the-incidence-risk-factors-and-case-fatality-rates-of-invasive-nontyphoidal-salmonella-ints-disease-in-africa-1966-to-2014
#20
Ifeanyi Valentine Uche, Calman A MacLennan, Allan Saul
This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases...
January 2017: PLoS Neglected Tropical Diseases
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