scholarly journals Antibody-Mediated Targeting of Antigens to Intestinal Aminopeptidase N Elicits Gut IgA Responses in Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Hans Van der Weken ◽  
Raquel Sanz Garcia ◽  
Niek N. Sanders ◽  
Eric Cox ◽  
Bert Devriendt
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Aminopeptidase N ◽  
Large Animal Model ◽  
Large Animal ◽  
Intestinal Immunity ◽  
Oral Vaccination ◽  
Antigen Presenting ◽  
Gut Pathogens

Many pathogens enter the host via the gut, causing disease in animals and humans. A robust intestinal immune response is necessary to protect the host from these gut pathogens. Despite being best suited for eliciting intestinal immunity, oral vaccination remains a challenge due to the gastrointestinal environment, a poor uptake of vaccine antigens by the intestinal epithelium and the tolerogenic environment pervading the gut. To improve uptake, efforts have focused on targeting antigens towards the gut mucosa. An interesting target is aminopeptidase N (APN), a conserved membrane protein present on small intestinal epithelial cells shown to mediate epithelial transcytosis. Here, we aimed to further optimize this oral vaccination strategy in a large animal model. Porcine APN-specific monoclonal antibodies were generated and the most promising candidate in terms of epithelial transcytosis was selected to generate antibody fusion constructs, comprising a murine IgG1 or porcine IgA backbone and a low immunogenic antigen: the F18-fimbriated E. coli tip adhesin FedF. Upon oral delivery of these recombinant antibodies in piglets, both mucosal and systemic immune responses were elicited. The presence of the FedF antigen however appeared to reduce these immune responses. Further analysis showed that F18 fimbriae were able to disrupt the antigen presenting capacity of intestinal antigen presenting cells, implying potential tolerogenic effects of FedF. Altogether, these findings show that targeted delivery of molecules to epithelial aminopeptidase N results in their transcytosis and delivery to the gut immune systems. The results provide a solid foundation for the development of oral subunit vaccines to protect against gut pathogens.

scholarly journals Niobium Carbide Loaded by Macrophage for Targeted Phototherapy Ablation of Breast Cancer

2020 ◽  
Author(s):  
Chiara Da Pieve ◽  
Gabriela Kramer Marek ◽  
Jolanta Saczko ◽  
Anant Shah ◽  
Florian Raes
Keyword(s):  
Animal Study ◽  
Human Body ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Niobium Carbide ◽  
Reactive Oxygen Species Generation ◽  
Large Animal Model ◽  
Large Animal ◽  
Photodynamic Effect

ABSTRACTAltough nanomaterial-mediated phototherapy has been extensively studied, the major antitumor success is limited to treating subcutaneous tumor on nude, lacking of clinically-relevant big animal study. Therefore, it is urgent to make further investigation on the typical big model, which is more closely related to the human body. In this work, niobium carbide (NbC) was selected as photoactive substance in virtue of its outstanding near infrared (NIR) absorption properties and resultantly NIR-triggered hyperthemia and reactive oxygen species generation for the synergetic photothermal and photodynamic effect. Moreover, macrophage was used as bio-carrier for the targeted delivery of NbC and the phagocytosis of macrophages was proved to be able to retain the photothermal/photodynamic effect of NbC. Resultantly, macrophage loaded NbC could realize complete removal of solid tumor on both of nude mice and big animal of rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) have been applied for monitoring the physiological evolutions of in vivo tumor post treatment, which clearly disclosed the photoablation process of tumor and provided a new way for the surveillance of tumor on the big animal study. Hence, large animal model study in this work presented higher clinical significance than the previous studies.SignificanceFindings show that niobium carbide carried by macrophages can be used for targeted phototherapy. At the same time, we applied the rabbit tumor model which is closer to the human body microenvironment.

scholarly journals Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Human Being

2021 ◽  
Author(s):  
Zhao Liu ◽  
Yuhang Tian ◽  
Shan Jiang ◽  
Haitao Shang ◽  
Kexin Chen ◽  
...  
Keyword(s):  
Animal Study ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Niobium Carbide ◽  
Reactive Oxygen Species Generation ◽  
Complete Removal ◽  
Large Animal Model ◽  
Large Animal ◽  
Photodynamic Effect

Abstract BackgroundAlthough nanomaterial-mediated phototherapy has been extensively studied, the major antitumor success is limited to treating subcutaneous tumor on nude, lacking of clinically-relevant big animal study. Therefore, it is urgent to make further investigation on the typical big model, which is more closely related to the human body. ResultsIn this work, niobium carbide (NbC) is selected as photoactive substance in virtue of its outstanding near infrared (NIR) absorption properties and resultantly NIR-triggered hyperthemia and reactive oxygen species generation for the synergetic photothermal and photodynamic effect. Moreover, macrophage is used as bio-carrier for the targeted delivery of NbC and the phagocytosis of macrophages is proved to be able to retain the photothermal/photodynamic effect of NbC. Resultantly, macrophage loaded NbC could realize complete removal of solid tumor on both of nude mice and big animal of rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) have been applied for monitoring the physiological evolutions of in vivo tumor post treatment, which clearly disclose the photoablation process of tumor and provide a new way for the surveillance of tumor on the big animal study. ConclusionHence, large animal model study in this work presents higher clinical significance than the previous studies.

Nanoparticles and Vaccine Development

2020 ◽  
Vol 8 (1) ◽  
pp. 6-21 ◽  
Author(s):  
Mehdi kheirollahpour ◽  
Mohsen Mehrabi ◽  
Naser Mohammadpour Dounighi ◽  
Mohsen Mohammadi ◽  
Alireza Masoudi
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Inorganic Nanoparticles ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Vaccine Antigens ◽  
Specific Receptors ◽  
Delivery Vehicles ◽  
Antigen Presenting

In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.

scholarly journals The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus

2020 ◽  
Vol 50 (11) ◽  
pp. 1712-1728
Author(s):  
Stefanie Schmidt ◽  
Friederike Ebner ◽  
Kerstin Rosen ◽  
Olaf Kniemeyer ◽  
Axel A. Brakhage ◽  
...  
Keyword(s):  
Animal Model ◽  
Immune Responses ◽  
Aspergillus Fumigatus ◽  
Large Animal Model ◽  
Large Animal ◽  
Domestic Pig

scholarly journals Distribution of droplets and immune responses after aerosol and intra-nasal delivery of influenza virus to the respiratory tract of pigs

2020 ◽  
Author(s):  
Veronica Martini ◽  
Michael Hinchcliffe ◽  
Elaine Blackshaw ◽  
Mary Joyce ◽  
Adam McNee ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Respiratory Infections ◽  
Influenza Virus Vaccine ◽  
Virus Antigen ◽  
Nasal Delivery ◽  
Large Animal Model ◽  
Large Animal

AbstractRecent evidence indicates that local immune responses and tissue resident memory T cells (TRM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccines to the respiratory tract in a large animal model, we investigated the distribution of droplets generated by a mucosal atomization device (MAD) and two vibrating mesh nebulizers (VMNs) and the immune responses induced by delivery of influenza virus by MAD in pigs. We showed that droplets containing the drug albuterol, a radiolabel (99mTc-DTPA) or a model influenza virus vaccine (S-FLU) have similar aerosol characteristics. 99mTc-DTPA scintigraphy showed that VMNs deliver droplets with uniform distribution throughout the lungs as well as the URT. Surprisingly MAD administration (1ml/nostril) also delivered a high proportion of the dose to the lungs, albeit concentrated in a small area. After MAD administration of influenza virus, antigen specific T cells were found at high frequency in nasal turbinates, trachea, broncho-alveolar lavage, lungs, tracheobronchial nodes and blood. We conclude that the pig is useful for investigating optimal targeting of vaccines to the respiratory tract.

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