Delving into the Latest Updates on UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH with Synapse

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1

项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的药物

Mefloquine Hydrochloride

盐酸甲氟喹

靶点

GJA8

作用机制

GJA8抑制剂

在研机构-

原研机构

Walter Reed Army Institute of Research

在研适应症-

非在研适应症

急性疟疾 [+4]

最高研发阶段撤市

首次获批国家/地区

美国

首次获批日期1989-05-02

100 项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的临床结果

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0 项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的专利（医药）

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32

项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的文献（医药）

2023-03-01·Cellular and Molecular Life Sciences

Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines

Article

作者: G Henshall, Isabelle ; Yeoh, Lee M ; Gilson, Paul R ; Wilson, Danny W ; Beeson, James G ; Weiss, Gretchen E ; Dutta, Sheetij ; Crabb, Brendan S ; Drew, Damien R

AbstractPlasmodium falciparum and P. vivax are the major causes of human malaria, and P. knowlesi is an important additional cause in SE Asia. Binding of apical membrane antigen 1 (AMA1) to rhoptry neck protein 2 (RON2) was thought to be essential for merozoite invasion of erythrocytes by Plasmodium spp. Our findings reveal that P. falciparum and P. vivax have diverged and show species-specific binding of AMA1 to RON2, determined by a β-hairpin loop in RON2 and specific residues in AMA1 Loop1E. In contrast, cross-species binding of AMA1 to RON2 is retained between P. vivax and P. knowlesi. Mutation of specific amino acids in AMA1 Loop1E in P. falciparum or P. vivax ablated RON2 binding without impacting erythrocyte invasion. This indicates that the AMA1–RON2-loop interaction is not essential for invasion and additional AMA1 interactions are involved. Mutations in AMA1 that disrupt RON2 binding also enable escape of invasion inhibitory antibodies. Therefore, vaccines and therapeutics will need to be broader than targeting only the AMA1–RON2 interaction. Antibodies targeting AMA1 domain 3 had greater invasion-inhibitory activity when RON2-loop binding was ablated, suggesting this domain is a promising additional target for vaccine development. Targeting multiple AMA1 interactions involved in invasion may enable vaccines that generate more potent inhibitory antibodies and address the capacity for immune evasion. Findings on specific residues for invasion function and species divergence and conservation can inform novel vaccines and therapeutics against malaria caused by three species, including the potential for cross-species vaccines.

2020-12-02·The American Journal of Tropical Medicine and Hygiene4区 · 医学

Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission

4区 · 医学

Review

作者: Hodges, James S. ; Hamre, Karen E. S. ; Ayodo, George ; Ondigo, Bartholomew N. ; John, Chandy C. ; Theisen, Michael ; Dutta, Sheetij

Immune correlates of protection against clinical malaria are difficult to ascertain in low-transmission areas because of the limited number of malaria cases. We collected blood samples from 5,753 individuals in a Kenyan highland area, ascertained malaria incidence in this population over the next 6 years, and then compared antibody responses to 11 Plasmodium falciparum vaccine candidate antigens in individuals who did versus did not develop clinical malaria in a nested case-control study (154 cases and 462 controls). Individuals were matched by age and village. Antigens tested included circumsporozoite protein (CSP), liver-stage antigen (LSA)-1, apical membrane antigen-1 FVO and 3D7 strains, erythrocyte-binding antigen-175, erythrocyte-binding protein-2, merozoite surface protein (MSP)-1 FVO and 3D7 strains, MSP-3, and glutamate-rich protein (GLURP) N-terminal non-repetitive (R0) and C-terminal repetitive (R2) regions. After adjustment for potential confounding factors, the presence of antibodies to LSA-1, GLURP-R2, or GLURP-R0 was associated with decreased odds of developing clinical malaria (odds ratio [OR], [95% CI] 0.56 [0.36-0.89], 0.56 [0.36-0.87], and 0.77 [0.43-1.02], respectively). Levels of antibodies to LSA-1, GLURP-R2, and CSP were associated with decreased odds of developing clinical malaria (OR [95% CI]; 0.61 [0.41-0.89], 0.60 [0.43-0.84], and 0.49 [0.24-0.99], for every 10-fold increase in antibody levels, respectively). The presence of antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 combined best-predicted protection from clinical malaria. Antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 are associated with protection against clinical malaria in a low-transmission setting. Vaccines containing these antigens should be evaluated in low malaria transmission areas.

2019-12-01·International Journal for Parasitology: Drugs and Drug Resistance2区 · 医学

Route map for the discovery and pre-clinical development of new drugs and treatments for cutaneous leishmaniasis

2区 · 医学

ReviewOA

作者: Sciotti, Richard ; Reguera, Rosa ; Arana, Byron ; Caridha, Diana ; Mowbray, Charles E ; Buffet, Pierre ; Rafati, Sima ; Vesely, Brian ; Croft, Simon L ; Kreishman-Deitrick, Mara ; Uliana, Silvia ; van Bocxlaer, Katrien

Although there have been significant advances in the treatment of visceral leishmaniasis (VL) and several novel compounds are currently in pre-clinical and clinical development for this manifestation of leishmaniasis, there have been limited advances in drug research and development (R & D) for cutaneous leishmaniasis (CL). Here we review the need for new treatments for CL, describe in vitro and in vivo assays, models and approaches taken over the past decade to establish a pathway for the discovery, and pre-clinical development of new drugs for CL. These recent advances include novel mouse models of infection using bioluminescent Leishmania, the introduction of PK/PD approaches to skin infection, and defined pre-clinical candidate profiles.

100 项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的药物交易

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100 项与 UNITED STATES ARMY WALTER REED ARMY INSTITUTE RESEARCH 相关的转化医学

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