Malaria: The Past and the Present

Microorganisms, Год журнала: 2019, Номер 7(6), С. 179 - 179

Опубликована: Июнь 21, 2019

Malaria is a severe disease caused by parasites of the genus Plasmodium, which transmitted to humans bite an infected female mosquito species Anopheles. remains leading cause mortality around world, and early diagnosis fast-acting treatment prevent unwanted outcomes. It most common in Africa some countries Asia, while developed world malaria occurs as imported from endemic areas. The sweet sagewort plant was used second century BC treat fever China. Much later, quinine started being antimalaria drug. A global battle against 1955, Croatia declared 1964 be year eradication malaria. World Health Organization carries out control program on scale, focusing local strengthening primary health care, disease, timely treatment, prevention. Globally, burden lower than ten years ago. However, last few years, there has been increase number cases world. moving towards targets established WHO, but that progress slowed down.

Язык: Английский

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HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure

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

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Malaria Vaccines: Recent Advances and New Horizons

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

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Malaria vaccines since 2000: progress, priorities, products

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

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A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses

Science, Год журнала: 2019, Номер 366(6470)

Опубликована: Окт. 31, 2019

Engineering better bnAbs A highly effective HIV vaccine has been the goal of vaccinologists for nearly 35 years. successful would need to induce broadly neutralizing antibodies (bnAbs) that are capable multiple strains (see Perspective by Agazio and Torres). Steichen et al. report a strategy in which first shot can lead immune responses generate desired bnAbs. By combining knowledge human antibody repertoires structure guide design, they validated candidate immunogens through functional preclinical testing. Saunders designed with differences binding strength bnAb precursors, enabled selection rare mutations after immunization. The promoted precursor maturation humanized mice macaques. Science , this issue p. eaax4380 eaay7199 ; see also 1197

Язык: Английский

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Challenges and strategies for developing efficacious and long-lasting malaria vaccines

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

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Advances and opportunities in malaria population genomics

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

Опубликована: Апрель 8, 2021

Язык: Английский

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RTS,S: the first malaria vaccine

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(1)

Опубликована: Янв. 3, 2022

The long road to vaccine developmentAfter more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended malaria RTS,S for widespread use among children living in endemic areas.Pioneering studies using rodent models directed by Ruth S. Nussenzweig at New York University School Medicine demonstrated late 1960s that immunization with attenuated sporozoites -the infective stage Plasmodium -induces immune responses protect against parasite infection (1).These also identified circumsporozoite protein (CSP), sporozoite-specific molecule recognized protective is antigen incorporated (2).The CSP expressed on surface different species contains a central domain tandem repeats represent approximately 30% entire sequence.Extensive experimental evidence indicates binding antibodies these immobilizes sporozoites, preventing hepatocytes, an obligatory this (Figure 1).The hepatitis B virus-like particle genetically fused portion repeat C-terminal region P. falciparum (3).

Язык: Английский

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Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria

New England Journal of Medicine, Год журнала: 2022, Номер 387(5), С. 397 - 407

Опубликована: Авг. 3, 2022

New approaches for the prevention and elimination of malaria, a leading cause illness death among infants young children globally, are needed.We conducted phase 1 clinical trial to assess safety pharmacokinetics L9LS, next-generation antimalarial monoclonal antibody, its protective efficacy against controlled human malaria infection in healthy adults who had never or received vaccine malaria. The participants L9LS either intravenously subcutaneously at dose mg, 5 20 mg per kilogram body weight. Within 2 6 weeks after administration both control underwent which they were exposed mosquitoes carrying Plasmodium falciparum (3D7 strain).No concerns identified. an estimated half-life 56 days, it linearity, with highest mean (±SD) maximum serum concentration (Cmax) 914.2±146.5 μg milliliter observed lowest Cmax 41.5±4.7 those intravenously; was 164.8±31.1 68.9±22.3 subcutaneously. A total 17 recipients infection. Of single 15 (88%) protected Parasitemia did not develop any intravenous L9LS. developed intravenously, subcutaneously, all through 21 days Protection conferred by seen concentrations as low 9.2 milliliter.In this small trial, administered infection, without evident concerns. (Funded National Institute Allergy Infectious Diseases; VRC 614 ClinicalTrials.gov number, NCT05019729.).

Язык: Английский

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Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali

New England Journal of Medicine, Год журнала: 2022, Номер 387(20), С. 1833 - 1842

Опубликована: Ноя. 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.).

Язык: Английский

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