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1.
Nat Commun ; 15(1): 7206, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174515

RESUMEN

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium.


Asunto(s)
Antígenos de Protozoos , Eritrocitos , Hígado , Proteínas de la Membrana , Ratones Endogámicos BALB C , Proteínas Protozoarias , Animales , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/metabolismo , Femenino , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Ratones , Humanos , Eritrocitos/parasitología , Eritrocitos/inmunología , Hígado/parasitología , Hígado/inmunología , Hígado/metabolismo , Vacunas contra la Malaria/inmunología , Malaria/inmunología , Malaria/parasitología , Malaria/prevención & control , Reacciones Cruzadas/inmunología , Plasmodium falciparum/inmunología , Plasmodium berghei/inmunología , Epítopos/inmunología , Hepatocitos/parasitología , Hepatocitos/inmunología , Hepatocitos/metabolismo , Plasmodium/inmunología , Merozoítos/inmunología , Merozoítos/metabolismo
2.
Sci Rep ; 12(1): 14044, 2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-35982212

RESUMEN

Nanostructures exhibiting optical resonances (so-called nanoantennas) have strong potential for applications in color printing and filtering with sub-wavelength resolution. While small scale demonstrations of these systems are interesting as a proof-of-concept, their large scale and volume fabrication requires deeper analysis and further development for industrial adoption. Here, we evaluate the color quality produced by large size nanoantenna arrays fabricated on a 12-in. wafer using deep UV immersion photolithography and dry etching processes. The color reproduction and quality are analyzed in context of the CIE color diagram, showing that a vivid and vibrant color palette, almost fully covering the sRGB color space, can be obtained with this mass-manufacturing-ready fabrication process. The obtained results, thus, provide a solid foundation for the potential industrial adoption of this emerging technology and expose the limits and challenges of the process.

3.
Opt Express ; 27(18): 26060-26069, 2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31510466

RESUMEN

The implementation of polarization controlling components enables additional functionalities of short-wave infrared (SWIR) imagers. The high-performance and mass-producible polarization controller based on Si metasurface is in high demand for the next-generation SWIR imaging system. In this work, we report the first demonstration of all-Si metasurface based polarizing bandpass filters (PBFs) on 12-inch wafers. The PBF achieves a polarization extinction ratio of above 10 dB in power within the passbands. Using the complementary metal-oxide-semiconductor (CMOS) compatible 193nm ArF deep ultra-violet (DUV) immersion lithography and inductively coupled plasma (ICP) etch processing line, a device yield of 82% is achieved.

4.
Opt Express ; 26(15): 19548-19554, 2018 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-30114125

RESUMEN

The demonstration of a color display metasurface on a 12-inch silicon wafer with critical dimension (CD) below 100 nm by complementary metal-oxide semiconductor (CMOS) compatible technology is reported for the first time. The 193 nm ArF deep UV immersion lithography is leveraged instead of electron beam lithography (EBL) to pattern the metasurface, which greatly improves the efficiency while keeping a high resolution. The demonstrated metasurface successfully generates the resonant modes and reflects the lights at resonance wavelengths, giving its display in red, green, and blue (RGB) colors. The wafer-level uniformities of CD and reflection characteristic of the metasurface are measured and analyzed. The experimental data show that they are well controlled in the fabrication process. The work provides a promising route towards mass production of dielectric metasurfaces.

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