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Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

Published on Dec 1, 2019in Nature Communications11.878
· DOI :10.1038/s41467-018-08265-9
Marianela C. Serradell3
Estimated H-index: 3
(CONICET: National Scientific and Technical Research Council),
Lucía L. Rupil3
Estimated H-index: 3
(CONICET: National Scientific and Technical Research Council)
+ 16 AuthorsHugo D. Luján23
Estimated H-index: 23
(CONICET: National Scientific and Technical Research Council)
Sources
Abstract
Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host’s intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines. Giardia lamblia express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host´s intestine. Here the authors show that stability and immunomodulatory properties of VSPs can be exploited to both protect and adjuvant vaccine antigens for oral administration.
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References73
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Abstract We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest c...
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Giardia lamblia is a human intestinal parasite and one of the most frequent enteric pathogen of companion animals. Clinical manifestations of giardiasis, such as diarrhoea, anorexia, weight loss and lethargy, have been associated with Giardia infections in both domestic and farm animals. A few anti-parasitic drugs are routinely used to treat giardiasis, but re-infections are common and drug-resistant strains have already been reported. Unfortunately, efficient vaccines against Giardia are not av...
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Fil: Gargantini, Pablo Ruben. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigacion y Desarrollo en Inmunologia y Enfermedades Infecciosas. Universidad Catolica de Cordoba. Centro de Investigacion y Desarrollo en Inmunologia y Enfermedades Infecciosas; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Catedra de Bioquimica y Biologia Molecular; Argentina
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