Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein DOI Creative Commons
Rama Raghunandan, Bryan T. Mayer, Yevel Flores-García

и другие.

Malaria Journal, Год журнала: 2020, Номер 19(1)

Опубликована: Март 17, 2020

New strategies are needed to reduce the incidence of malaria, and promising approaches include development vaccines monoclonal antibodies (mAbs) that target circumsporozoite protein (CSP). To select best candidates speed development, it is essential standardize preclinical assays measure potency such interventions in animal models.Two assay configurations were studied using transgenic Plasmodium berghei expressing falciparum full-length protein. The measured (1) reduction parasite infection liver (liver burden) following an intravenous (i.v) administration sporozoites (2) protection from parasitaemia mosquito bite challenge. Two human CSP mAbs, AB311 AB317, compared for their ability inhibit infection. Multiple independent experiments conducted define variability resultant impact on discriminate differences mAb functional activity.Overall, produced highly consistent results all individual showed greater activity AB317 as calculated by dose required 50% inhibition (ID50) well serum concentration (IC50). data then used model experimental designs with adequate statistical power rigorously screen, compare, rank order novel anti-CSP mAbs.The indicate vivo described here can provide reliable information comparing mAbs. also guidance regarding selection appropriate design, selection, group sizes.

Язык: Английский

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

305

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

224

Malaria prevention: from immunological concepts to effective vaccines and protective antibodies DOI Creative Commons
Ian A. Cockburn, Robert A. Seder

Nature Immunology, Год журнала: 2018, Номер 19(11), С. 1199 - 1211

Опубликована: Окт. 12, 2018

Development of a malaria vaccine remains critical priority to decrease clinical disease and mortality facilitate eradication. Accordingly, RTS,S, protein-subunit vaccine, has completed phase III trials confers ~30% protection against infection over 4 years. Whole-attenuated-sporozoite viral-subunit vaccines induce between 20% 100% controlled human infection, but there is limited published evidence date for durable, high-level efficacy (>50%) natural exposure. Importantly, fundamental scientific advances related the potency, durability, breadth location immune responses will be required improving with these other approaches. In this Review, we focus on current understanding immunological mechanisms from animal models studies, how data should inform development next-generation vaccines. Furthermore, introduce concept using passive immunization monoclonal antibodies as new approach prevent eliminate malaria.

Язык: Английский

Процитировано

156

Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response DOI Creative Commons
Hayley A. McNamara, Azza H. Idris, Henry J. Sutton

и другие.

Cell Host & Microbe, Год журнала: 2020, Номер 28(4), С. 572 - 585.e7

Опубликована: Июль 21, 2020

Язык: Английский

Процитировано

138

Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy DOI Creative Commons
Carlota Dobaño, Héctor Sanz, Hermann Sorgho

и другие.

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Май 15, 2019

RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy African children and infants. In cohort of 1028 subjects from one low (Bagomoyo) two high (Nanoro, Kintampo) transmission sites, we analysed IgG plasma/serum concentration avidity to CSP (NANP-repeat C-terminal domains) after 3-dose vaccination against time clinical events during 12-months. Here report that induces substantial increases levels pre- post-vaccination (p < 0.001), higher NANP than C-terminus (2855 vs 1297 proportional change between means), concentrations avidities infants 0.001). Baseline are elevated cases controls Both, magnitude (hazard ratio [95% confidence interval] 0.61 [0.48-0.76]) (0.07 [0.05-0.90]) significantly associated efficacy. the emerges as significant contributor RTS,S/AS01E-mediated protection.

Язык: Английский

Процитировано

130

A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver DOI Creative Commons
Lawrence Wang,

Lais S. Pereira,

Yevel Flores-García

и другие.

Immunity, Год журнала: 2020, Номер 53(4), С. 733 - 744.e8

Опубликована: Сен. 17, 2020

Язык: Английский

Процитировано

127

Antibodies against Plasmodium falciparum malaria at the molecular level DOI
Jean‐Philippe Julien, Hedda Wardemann

Nature reviews. Immunology, Год журнала: 2019, Номер 19(12), С. 761 - 775

Опубликована: Авг. 28, 2019

Язык: Английский

Процитировано

99

Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs DOI
Rajagopal Murugan, S.W. Scally, Giulia Costa

и другие.

Nature Medicine, Год журнала: 2020, Номер 26(7), С. 1135 - 1145

Опубликована: Май 25, 2020

Язык: Английский

Процитировано

84

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies DOI Creative Commons
Pankaj Chandley, Ravikant Ranjan, Sudhir Kumar

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 13

Опубликована: Янв. 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.

Язык: Английский

Процитировано

26

Structural Basis of Enhanced Crystallizability Induced by a Molecular Chaperone for Antibody Antigen-Binding Fragments DOI
June Ereño‐Orbea,

Taylor Sicard,

Hong Cui

и другие.

Journal of Molecular Biology, Год журнала: 2017, Номер 430(3), С. 322 - 336

Опубликована: Дек. 22, 2017

Язык: Английский

Процитировано

67