Novel approaches to enable equitable access to monoclonal antibodies in low- and middle-income countries DOI Creative Commons
Shelly Malhotra, A.G.W. Cameron, Dzintars Gotham

et al.

PLOS Global Public Health, Journal Year: 2024, Volume and Issue: 4(7), P. e0003418 - e0003418

Published: July 1, 2024

Monoclonal antibodies (mAbs) are revolutionizing management of non-communicable diseases in high-income countries and increasingly being advanced for a range infectious (IDs). However, access to existing mAbs is limited low- middle-income (LMICs), investment developing fit-for-purpose IDs that disproportionately affect LMICs has been limited. Underlying these barriers systemic challenges, including lack commercial incentives target LMIC markets complexity manufacturing regulatory processes. Novel strategies needed overcome mAbs. We outline key areas where new approaches could address barriers, based on multistakeholder consultation March 2023. Three disease-market archetypes identified guide thinking about business models tailored different contexts. New incentivize development ID ensure optimized with product profile cost goods enable use diverse settings. Lessons can be applied from voluntary licensing partnerships have shown success catalysing affordable supply diseases. Technology transfer will expand research capacity sustainable diversified supply. Improved market intelligence, demand aggregation mechanisms, portfolio-based used de-risk establish ecosystem robust technology may reduce data requirements timelines biosimilar approvals. Trailblazer products, coordinated “end-to-end” support funders, demonstrate proof concept pathways accessible across broader LMICs. Research funders; local, regional, global health agencies; and, private sector partners should commit implementing innovative end-to-end equitable

Language: Английский

Climate Change and Vectorborne Diseases DOI Creative Commons
Madeleine C. Thomson, Lawrence R. Stanberry

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(21), P. 1969 - 1978

Published: Nov. 24, 2022

T he effects of climate change are widespread and rapidly intensifying largely driven by greenhouse-gas emissions from burning fossil fuels. 1 Global mean temperatures have already increased 1.1°C since 1900, with most the having occurred in past 50 years.The extent is extreme highland polar regions (Fig. 1), tropical creeping closer to thermal limits many organisms.Given current policies actions, a warming 2.5°C 2.9°C or more end this century expected. 2arming other manifestations -including changes precipitation, flooding some areas drought others -have important implications for vectorborne diseases through their on pathogens, vectors, hosts, as well our ability prevent treat these 2).Yet attributing distribution frequency vectors challenging because factors, including land-use changes, 3 abundance reservoir 4 control measures, 5 also contribute changes.Furthermore, it may be difficult distinguish between natural variability human-influenced change, 6 although scientific techniques do so emerging.Despite complexities, clear that components disease systems, highly responsive varied environments they inhabit observed rates at given locations often associated concomitant local climate.For example, affect behavior, physiologic characteristics, life history both pathogens behavior hosts definitive hosts.The interactions among temperature, vector, pathogen can risk human-to-human spread spillover humans hosts.Thermal performance curves illustrate ways which temperature affects physiological traits determine rate susceptible population.These commonly used predict potential rising resulting systems. 7Curves individual system must overlap order transmission occur.Thermal adaptation, acclimation climate, potentially shift tolerance limits, expansion geographic range certain diseases.Depending adapt, no longer carry new ones climate-mediated ecosystem bring different human together.

Language: Английский

Citations

107
Antimalarial drug discovery: progress and approaches DOI
Jair L. Siqueira-Neto, Kathryn J. Wicht, Kelly Chibale

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(10), P. 807 - 826

Published: Aug. 31, 2023

Language: Английский

Citations

101
Malaria DOI
Jeanne Rini Poespoprodjo, Nicola Davies, Daniel Ansong

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 402(10419), P. 2328 - 2345

Published: Nov. 2, 2023

Language: Английский

Citations

95
The emergence of artemisinin partial resistance in Africa: how do we respond? DOI Open Access
Philip J. Rosenthal, Victor Asua, Jeffrey A. Bailey

et al.

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(9), P. e591 - e600

Published: March 26, 2024

Language: Английский

Citations

51
Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria DOI Open Access
Kassoum Kayentao, Aissata Ongoïba,

Anne C Preston

et al.

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
Malaria vaccines: a new era of prevention and control DOI
Patrick E. Duffy,

J. Patrick Gorres,

Sara A. Healy

et al.

Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(12), P. 756 - 772

Published: July 18, 2024

Language: Английский

Citations

32
A candidate antibody drug for prevention of malaria DOI Creative Commons
Katherine L. Williams,

Steve Guerrero,

Yevel Flores-García

et al.

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
Sporozoite immunization: innovative translational science to support the fight against malaria DOI Creative Commons
Thomas L. Richie, L. W. Preston Church,

Tooba Murshedkar

et al.

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
Updates on Malaria Epidemiology and Prevention Strategies DOI Creative Commons
Marta Sanz, Pedro Berzosa, Francesca Norman

et al.

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
Vaccines and monoclonal antibodies: new tools for malaria control DOI
Kazutoyo Miura, Yevel Flores-García, Carole A. Long

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: April 24, 2024

SUMMARYMalaria remains one of the biggest health problems in world. While significant reductions malaria morbidity and mortality had been achieved from 2000 to 2015, favorable trend has stalled, rather increases cases are seen multiple areas. In 2022, there were 249 million estimated cases, 608,000 malaria-related deaths, mostly infants children aged under 5 years, globally. Therefore, addition expansion existing anti-malarial control measures, it is critical develop new tools, such as vaccines monoclonal antibodies (mAbs), fight malaria. last 2 first second vaccines, both targeting

Language: Английский

Citations

12