Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential DOI Creative Commons
Kara A. Moser, Elliott F. Drábek, Ankit Dwivedi

и другие.

Genome Medicine, Год журнала: 2020, Номер 12(1)

Опубликована: Янв. 8, 2020

Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation these results and understanding their relevance vaccine efficacy hampered by lack knowledge on genetic differences between how strains are related parasites endemic regions.Whole genome sequencing using long-read (Pacific Biosciences) short-read (Illumina) platforms was conducted generate de novo assemblies for strain, NF54, used (7G8 from Brazil, NF166.C8 Guinea, NF135.C10 Cambodia). The were characterize sequences each strain relative reference 3D7 (a clone NF54) genome. Strains compared other a collection isolates (sequenced as part this study or public repositories) South America, sub-Saharan Africa, Southeast Asia.While few variants detected we identified tens thousands NF54 three strains. These include SNPs, indels, small structural that fall regulatory immunologically important regions, including transcription factors (such PfAP2-L PfAP2-G) pre-erythrocytic antigens may be key Additionally, directly contributed diversity regions genomes through silico CD8+ T cell epitope predictions. Of all had highest number unique predicted when NF54. Comparison global revealed four representative geographic origin despite long-term culture adaptation; note, is an admixed population, not recently formed subpopulations resistant artemisinin-based therapies present Greater Mekong Sub-region.These will assist CHMI.

Язык: Английский

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability DOI Creative Commons
Philip J. M. Brouwer, Tom G. Caniels, Karlijn van der Straten

и другие.

Science, Год журнала: 2020, Номер 369(6504), С. 643 - 650

Опубликована: Июнь 15, 2020

Sites of vulnerability in SARS-CoV-2 Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool treating disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show the patients had strong immune responses against viral spike protein, a complex binds to receptors on host cell. A subset was able virus. Competition and electron microscopy studies showed these target diverse epitopes spike, with two most potent targeting domain receptor. Science , this issue p. 643

Язык: Английский

Процитировано

1282
Broad betacoronavirus neutralization by a stem helix–specific human antibody DOI Creative Commons
Dora Pinto, Maximilian M. Sauer,

Nadine Czudnochowski

и другие.

Science, Год журнала: 2021, Номер 373(6559), С. 1109 - 1116

Опубликована: Авг. 3, 2021

Targeting a range of betacoranaviruses In the past 20 years, three highly pathogenic β-coronaviruses have crossed from animals to humans, including most recent: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A spike protein that decorates these viruses has an S1 domain binds host cell receptors and S2 fuses viral membranes allow entry. The is target many neutralizing antibodies but more genetically variable than S2, can exert selective pressure, leading resistant variants. Pinto et al . identified five monoclonal interact with helix in domain. broadly antibody inhibited all β-coronavirus subgenera reduced burden hamsters infected SARS-CoV-2. —VV

Язык: Английский

Процитировано

364
HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure DOI Creative Commons
Peter D. Kwong, John R. Mascola

Immunity, Год журнала: 2018, Номер 48(5), С. 855 - 871

Опубликована: Май 1, 2018

HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies the envelope (Env) trimer, sole viral antigen on virion surface. Antibodies isolated from HIV-1-infected donors, however, have shown recognize all major exposed regions of prefusion-closed Env and emerging understanding immunological structural characteristics these epitopes they is enabling new approaches design. Antibody lineage-based design creates immunogens that activate naive ancestor-B cell a target antibody lineage mature intermediate-B cells toward effective neutralization, with proof principle achieved select HIV-1-neutralizing lineages in human-gene knock-in mouse models. Epitope-based involves engineering sites vulnerability as defined recognition antibodies, cross-reactive elicited animal Both epitope-based are being readied for human clinical trials.

Язык: Английский

Процитировано

308
Malaria Vaccines: Recent Advances and New Horizons DOI Creative Commons
Simon J. Draper,

Brandon K. Sack,

C. Richter King

и другие.

Cell Host & Microbe, Год журнала: 2018, Номер 24(1), С. 43 - 56

Опубликована: Июль 1, 2018

The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum P. vivax remains a key priority. Decades endeavor have taught that achieving this goal will be challenging; however, recent innovation in vaccine research diverse pipeline novel candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic aiming licensure coming years, it is important to reflect on how next-generation approaches can improve their success. Here we review latest seek prevent infection, disease, transmission highlight some major underlying immunological molecular mechanisms protection. synthesis rational antigen selection, immunogen design, immunization strategies induce quantitatively qualitatively improved immune effector offers promise sustained high-level

Язык: Английский

Процитировано

306
Malaria vaccines since 2000: progress, priorities, products DOI Creative Commons
Patrick E. Duffy,

J. Patrick Gorres

npj Vaccines, Год журнала: 2020, Номер 5(1)

Опубликована: Июнь 9, 2020

Malaria vaccine development entered a new era in 2015 when the pre-erythrocytic

Язык: Английский

Процитировано

225
Challenges and strategies for developing efficacious and long-lasting malaria vaccines DOI Creative Commons
James G. Beeson, Liriye Kurtovic, Carlota Dobaño

и другие.

Science Translational Medicine, Год журнала: 2019, Номер 11(474)

Опубликована: Янв. 9, 2019

New knowledge and strategies are emerging to enable the development of an efficacious long-lasting vaccine against malaria.

Язык: Английский

Процитировано

184
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies DOI Creative Commons
Jun Siong Low, Josipa Jerak, M. Alejandra Tortorici

и другие.

Science, Год журнала: 2022, Номер 377(6607), С. 735 - 742

Опубликована: Июль 12, 2022

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind all human-infecting proteins from severe acute respiratory syndrome 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide acquire affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against alpha- betacoronaviruses, including animal coronaviruses WIV-1 PDF-2180. Two selected also neutralize Omicron BA.1 BA.2 authentic viruses reduce burden pathology vivo. Structural functional analyses showed peptide–specific bound with different modalities cryptic epitope hidden prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme (ACE2) or ACE2-mimicking mAbs.

Язык: Английский

Процитировано

148
Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2 DOI Open Access
Xiaoyu Sun, Chunyan Yi, Yuanfei Zhu

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(7), С. 1063 - 1074

Опубликована: Июнь 30, 2022

Язык: Английский

Процитировано

118
Advances and opportunities in malaria population genomics DOI Open Access
Daniel E. Neafsey, Aimee R. Taylor, Bronwyn MacInnis

и другие.

Nature Reviews Genetics, Год журнала: 2021, Номер 22(8), С. 502 - 517

Опубликована: Апрель 8, 2021

Язык: Английский

Процитировано

117
A candidate antibody drug for prevention of malaria DOI Creative Commons
Katherine L. Williams,

Steve Guerrero,

Yevel Flores-García

и другие.

Nature Medicine, Год журнала: 2024, Номер 30(1), С. 117 - 129

Опубликована: Янв. 1, 2024

Abstract Over 75% of malaria-attributable deaths occur in children under the age 5 years. However, first malaria vaccine recommended by World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important efforts to eradicate malaria. Here we characterize circulating B cell repertoires 45 vaccinees and discover antibodies development as potential therapeutics. We generated >28,000 antibody sequences tested 481 binding activity 125 antimalaria vivo. Through these analyses identified correlations suggesting that Plasmodium falciparum circumsporozoite protein, target antigen RTS,S/AS01, may induce immunodominant responses limit more protective, but subdominant, responses. Using studies, mouse models, biomanufacturing assessments protein stability assays, selected AB-000224 AB-007088 advancement a clinical lead backup. engineered variable domains (Fv) both enable low-cost manufacturing at scale distribution populations, alignment with WHO’s preferred product guidelines. The clone optimal drug property profile, MAM01, was advanced into development.

Язык: Английский

Процитировано

20