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Pineyro, P.

Publications and source records attributed to Pineyro, P..

2 recordsLinked to original sources

Establishment and Characterization of Novel Canine Organoids with Organ-Specific Physiological Similarity

Organoids are 3-dimensional (3D) stem cell-derived cell culture lines that offer a variety of technical advantages compared to traditional 2-dimensional (2D) cell cultures. Although murine models have proved useful in biomedical research, rodent models often fail to adequately mimic human physiology and disease progression, resulting in poor preclinical prediction of therapeutic drug efficacy and toxicity. With the advent of organoid technology, many of these challenges can be overcome. Previously, the use of canine organoids in drug testing and disease modeling was limited to organoids originating from the intestine, liver, kidney, lung, and urinary bladder. Here, we report the cultivation, maintenance, and molecular characterization of two novel adult-stem cell-derived canine organoid cell lines, including the endometrium and pancreas, in addition to previously reported bladder, lung, and liver organoids from two genetically related canines. Five tissues and organoid lines from each donor were characterized using bulk RNA-seq, allowing for a unique, multi-organ comparison between these two individuals and identification of specific cell types such as glandular epithelial cells in endometrial organoids.

genetics↗

Protective efficacy of an orf virus-vector encoding the hemmagglutinin and the nucleoprotein of influenza A virus in swine

Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses constant challenges to public health due to its zoonotic potential. Thus effective IAV-S vaccines are highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or both the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs. Notably, although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S specific proliferating T cells secreting IFN-{gamma} upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in better protective efficacy as evidenced by reduced virus shedding in nasal secretions and reduced viral load in the lung. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine. ImportanceEffective influenza A virus (IAV-S) vaccines capable of providing robust protection to genetically diverse IAV-S in swine are lacking. Here, we explored the potential of orf virus based vectors expressing the hemagglutining (HA) or both the HA and the nucleoprotein (NP) genes of influena A virus (IAV-S) in eliciting protection against IAV-S in pigs. We observed that both recombinant viruses elicited IAV-S-specific humoral and cell-mediated immune responses in pigs. Addition of the NP and co-expression of this protein with HA, another major influenza protective antigen, resulted in higher T cell responses which presumably led to better protection in OV-HA-NP immunized animals, as evidenced by lower levels of virus shedding and viral load in lungs. This study highlights the the potential of ORFV as a vector platform for vaccine delivery against IAV-S. Results here provide the foundation for future development of broadly protective ORFV-based vectors for IAV-S for use in swine.

immunology↗