Nature Immunology, Journal Year: 2024, Volume and Issue: 25(9), P. 1530 - 1545
Published: Aug. 28, 2024
Language: Английский
Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(10), P. 807 - 826
Published: Aug. 31, 2023
Language: Английский
Citations
101
The Lancet, Journal Year: 2023, Volume and Issue: 402(10419), P. 2328 - 2345
Published: Nov. 2, 2023
Language: Английский
Citations
95
New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(20), P. 1833 - 1842
Published: Nov. 1, 2022
CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in phase 1 clinical trial. Whether can prevent P. region which the endemic unknown.We conducted 2 trial assess safety and efficacy of single intravenous infusion healthy adults Mali over 6-month malaria season. In Part A, assessed at three escalating dose levels. B, participants were randomly assigned (in 1:1:1 ratio) receive 10 mg per kilogram body weight, 40 kilogram, or placebo. The primary end point, time-to-event analysis, first detected on blood-smear examination, performed least every weeks for 24 weeks. At enrollment, all received artemether-lumefantrine clear possible infection.In 330 underwent randomization; 110 each group. risk moderate headache 3.3 times as high with infections examination 39 (35.5%) who 20 (18.2%) 86 (78.2%) 6 months, compared placebo 88.2% (adjusted 95% confidence interval [CI], 79.3 93.3; P<0.001), 75.0% CI, 61.0 84.0; P<0.001).CIS43LS protective season without evident concerns. (Funded by National Institute Allergy Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).
Language: Английский
Citations
82
New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 390(17), P. 1549 - 1559
Published: April 29, 2024
BackgroundSubcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether administered subcutaneously can protect children from P. region where this organism is endemic unclear.MethodsWe conducted 2 trial Mali to assess safety and efficacy subcutaneous 6 10 years age over 6-month malaria season. In part A trial, was assessed at three dose levels adults, followed by assessment two children. B were randomly assigned, 1:1:1 ratio, receive 150 mg L9LS, 300 or placebo. The primary end point, time-to-event analysis, first infection, as detected on blood smear performed least every weeks for 24 weeks. secondary point episode clinical malaria, analysis.ResultsNo concerns identified dose-escalation (part A). B, 225 underwent randomization, with 75 assigned each group. No B. occurred 36 participants (48%) 150-mg group, 30 (40%) 300-mg 61 (81%) placebo compared placebo, 66% (adjusted confidence interval [95% CI], 45 79) 70% 95% CI, 50 82) (P<0.001 both comparisons). Efficacy 67% 39 77% 55 89) comparisons).ConclusionsSubcutaneous protective period months. (Funded National Institute Allergy Infectious Diseases; ClinicalTrials.gov number, NCT05304611.)
Language: Английский
Citations
36
Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(12), P. 756 - 772
Published: July 18, 2024
Language: Английский
Citations
32
Nature Medicine, Journal Year: 2024, Volume and Issue: 30(1), P. 117 - 129
Published: Jan. 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.
Language: Английский
Citations
20
Expert Review of Vaccines, Journal Year: 2023, Volume and Issue: 22(1), P. 964 - 1007
Published: Aug. 11, 2023
Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children pregnant women sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for
Language: Английский
Citations
30
Current Infectious Disease Reports, Journal Year: 2023, Volume and Issue: 25(7), P. 131 - 139
Published: June 8, 2023
The objective of this review was to provide an update on recent malaria epidemiology, both globally and in non-endemic areas, identify the current distribution repercussions genetically diverse Plasmodium species summarize recently implemented intervention prevention tools. Notable changes epidemiology have occurred years, with increase number total cases deaths during 2020–2021, part attributed COVID-19 pandemic. emergence artemisinin-resistant new areas expanding parasites harbouring deletions pfhrp2/3 genes been concerning. New strategies curb burden infection, such as vaccination, certain endemic their performance is currently being evaluated. Inadequate control regions may effect imported measures prevent re-establishment transmission malaria-free are essential. Enhanced surveillance investigation spp. genetic variations will contribute successful diagnosis treatment future. Novel for integrated One Health approach should also be strengthened.
Language: Английский
Citations
28
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13
Published: Jan. 4, 2023
Malaria is a global infectious disease that remains leading cause of morbidity and mortality in the developing world. Multiple environmental host parasite factors govern clinical outcomes malaria. The immune response against Plasmodium heterogenous stage-specific both human mosquito vector. virulence predominantly associated with its ability to evade host’s response. Despite availability drug-based therapies, parasites can acquire drug resistance due high antigenic variations allelic polymorphisms. lack licensed vaccines infection necessitates development effective, safe successful therapeutics. To design an effective vaccine, it important study evasion strategies proteins, which are targets This review provides overview defense mechanisms during infection. Furthermore, we also summarize discuss current progress various anti-malarial vaccine approaches, along antibody-based therapy involving monoclonal antibodies, research advancements host-directed therapy, together open new avenues for novel immunotherapies malaria transmission.
Language: Английский
Citations
26
Cell, Journal Year: 2024, Volume and Issue: 187(18), P. 4964 - 4980.e21
Published: July 25, 2024
The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against disease-causing blood stage of malaria. However, features human vaccine-induced antibody response that confer potent inhibition malaria parasite invasion into red cells are not well defined. Here, we characterize 236 IgG monoclonal antibodies, derived from 15 donors, induced by most advanced PfRH5 vaccine. We define antigenic landscape this molecule establish epitope specificity, association rate, intra-PfRH5 interactions key determinants functional anti-parasitic potency. In addition, identify a germline gene combination results in an exceptionally class demonstrate its prophylactic potential to protect P. challenge vivo. This comprehensive dataset provides framework guide rational design next-generation antibodies blood-stage
Language: Английский
Citations
15