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Oral administration of engineered yeast produced H5HA-based vaccines

ABSTRACT: H5N8 influenza virus is a highly pathogenic pathogen for the poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches. In this study, we developed three HA gene-based yeast vaccines and our experimental results demonstrated that all of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided protective efficacy partially due to the high dose of H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccines reshaped the immune cell microenvironment in bursa of Fabriciu to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccines increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidences for further clinical use of these engineered yeast vaccines in poultry.

ORGANISM(S): Gallus gallus

PROVIDER: GSE220714 | GEO | 2023/01/01

REPOSITORIES: GEO

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Project description:While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines. 64 samples of IL4 DC, and 64 samples of monocytes stimulated by media (controls, designated 1 and 2 to indicate biological replicates), Menomune (Neisseiria meningitis vaccine, MGL), Fluzone 09-10 (Influenza vaccine, FZ), Havrix (Hepatitis A vaccine, HEPA), Ixiaro (Japanese encephalitis vaccine, JPE), ActHib (Haemophilus influenza vaccine, HIB) and Pneumovax (Pneumococcus vaccine, PVX), Engerix-B (Hepatitis B vaccine, HEPB), Zostavax (Herpes Zoster vaccine, HER), and Gardasil (Human Papilloma virus vaccine, HPV), LPS, Ipol (Polio vaccine, POL), Rabies vaccine (RAB), toxoid-based vaccine (TDAP), Varivax (Varicella vaccine, VAR)

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Oral administration of engineered yeast produced H5HA-based vaccines

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