scholarly journals Global selection of Plasmodium falciparum virulence antigen expression by host antibodies

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Abdirahman I. Abdi ◽  
George M. Warimwe ◽  
Michelle K. Muthui ◽  
Cheryl A. Kivisi ◽  
Esther W. Kiragu ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merricka C. Livingstone ◽  
Alexis A. Bitzer ◽  
Alish Giri ◽  
Kun Luo ◽  
Rajeshwer S. Sankhala ◽  
...  

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Li-Yun Lin ◽  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Dong-De Xie ◽  
Jiang-Tao Chen ◽  
...  

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.


2002 ◽  
Vol 45 (1) ◽  
pp. 155-167 ◽  
Author(s):  
Aleida Vazquez-Macias ◽  
Perla Martinez-Cruz ◽  
Maria Cristina Castaneda-Patlan ◽  
Christine Scheidig ◽  
Jurg Gysin ◽  
...  

2012 ◽  
Vol 5 (4) ◽  
pp. 517-525 ◽  
Author(s):  
Patricia Henríquez Rodríguez ◽  
Jesús B. Alonso Hernández ◽  
Miguel A. Ferrer Ballester ◽  
Carlos M. Travieso González ◽  
Juan R. Orozco-Arroyave

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Patience Nayebare ◽  
Victor Asua ◽  
Melissa D. Conrad ◽  
Richard Kajubi ◽  
Abel Kakuru ◽  
...  

ABSTRACT Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of Plasmodium falciparum genetic polymorphisms that alter susceptibility to these drugs. The prevalence of known genetic polymorphisms associated with altered drug susceptibility was determined in parasitemic samples, including 375 collected before IPTp drugs were administered, 125 randomly selected from those receiving SP, and 80 from those receiving DP. For women receiving DP, the prevalence of mixed/mutant sequences was greater in samples collected during IPTp than that in samples collected prior to the intervention for PfMDR1 N86Y (20.3% versus 3.9%; P < 0.001), PfMDR1 Y184F (73.0% versus 53.0%; P < 0.001), and PfCRT K76T (46.4% versus 24.0%; P < 0.001). Considering SP, prior to IPTp, the prevalence of all 5 common antifolate mutations was over 92%, and this prevalence increased following exposure to SP, although none of these changes were statistically significant. For two additional mutations associated with high-level SP resistance, the prevalence of PfDHFR 164L (13.7% versus 4.0%; P = 0.004), but not PfDHPS 581G (1.9% versus 3.0%; P = 0.74), was greater in samples collected during IPTp compared to those collected before the intervention. Use of IPTp in Uganda selected for parasites with mutations associated with decreased susceptibility to IPTp regimens. Thus, a potential drawback of IPTp is selection of parasites with decreased drug susceptibility.


2005 ◽  
Vol 1 (3) ◽  
pp. e26 ◽  
Author(s):  
Peter C Bull ◽  
Matthew Berriman ◽  
Sue Kyes ◽  
Michael A Quail ◽  
Neil Hall ◽  
...  

1979 ◽  
Vol 9 (1) ◽  
pp. 465-475 ◽  
Author(s):  
Tina Dalianis ◽  
George Klein ◽  
Birger Andersson

2019 ◽  
Vol 30 (3) ◽  
pp. 376-385 ◽  
Author(s):  
Dian Yu ◽  
Xiao Xiao ◽  
Douglas K. Bemis ◽  
Steven L. Franconeri

Across the natural world as well as the artificial worlds of maps, diagrams, and data visualizations, feature similarity (e.g., color and shape) links spatially separate areas into sets. Despite a century of study, it is yet unclear what mechanism underlies this gestalt similarity grouping. One recent proposal is that similarity grouping—for example, seeing a red, vertical, or square group—is just global selection of those features. Although parsimonious, this account makes the counterintuitive prediction that similarity grouping is strictly serial: A green group cannot be constructed at the same time as a red group. We tested this prediction with a novel measure—a grouping illusion within number-estimation tasks that should work only if participants simultaneously construct groups—and found the strongest evidence yet in favor of serial feature-based attention ( Ns = 14, 12, and 12 for Experiment 1, Experiment 2, and Experiment 3, respectively).


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