Mesenchymal stem cells as vaccine adjuvants and methods for using the same
Inventors
Hare, Joshua M. • LANDIN, Ana Marie
Assignees
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Publication Number
US-11975068-B2
Publication Date
2024-05-07
Expiration Date
Abstract
The present invention provides a method of enhancing an immune response to a vaccine by administering a vaccine and a population of isolated allogeneic human mesenchymal stem cells. The present invention also provides kits comprising a vaccine in a first container and a population of isolated allogeneic human mesenchymal stem cells in a second container.
Core Innovation
A method is described for enhancing a subject’s immune response to a vaccine or inducing an immune response in a subject whose immune system did not previously react to the vaccine. The method identifies a human subject exhibiting inflammaging and the syndrome of aging frailty and in need of treatment with a vaccine combined with an adjuvant. The adjuvant comprises allogeneic human mesenchymal stem cells that are isolated and have not been genetically manipulated.
The vaccine and the adjuvant are administered concurrently or sequentially, and the adjuvant is administered in an amount effective at reducing inflammaging. The approach is directed to subjects whose immune system did not previously react to the vaccine and is intended to reduce inflammaging while enhancing or inducing immune responses. The described immune context includes immune readouts associated with B-cell and T-cell compartments.
Embodiments include vaccine antigens such as inactivated viruses and live-attenuated viruses, including an inactivated influenza virus, and administration can be systemic/parenteral. The document further describes cell-source options, marker exclusions such as STRO-1 negative and CD45 negative, exclusion of fibroblast surface markers including fibroblast morphology, and kit formats in which the vaccine and mesenchymal stem cells are provided in separate containers, optionally including cryopreserved mesenchymal stem cells with a dilution buffer.
Claims Coverage
The document includes one independent claim centered on identifying a human subject with inflammaging and aging frailty and administering a vaccine with an adjuvant of isolated allogeneic human mesenchymal stem cells that have not been genetically manipulated, in an amount effective at reducing inflammaging. The remaining claims refine this framework with specific inventive features regarding vaccine antigen form, immune biomarker changes, dosing and administration parameters, and mesenchymal stem cell and donor-handling constraints.
Subject selection for inflammaging and aging frailty
Identifying a human subject exhibiting inflammaging and the syndrome of aging frailty and in need of treatment with a vaccine in combination with an adjuvant comprising allogeneic human mesenchymal stem cells.
Concurrent or sequential vaccine and MSC adjuvant administration
Administering to the subject concurrently or sequentially the vaccine and the adjuvant.
Isolated allogeneic human mesenchymal stem cells not genetically manipulated
The adjuvant is a population of isolated allogeneic human mesenchymal stem cells that have not been genetically manipulated.
Adjuvant amount effective at reducing inflammaging
Administering the allogeneic human mesenchymal cells in an amount effective at reducing inflammaging.
Vaccine comprising inactivated viruses
The method includes a vaccine that comprises one or more inactivated viruses.
Reduction of intracellular TNF-α in B cells
After administering the adjuvant, intracellular TNF-α expression in B cells decreases by at least two-fold compared with pre-administration levels.
Adjuvant dose of about 100×10^6 mesenchymal stem cells
The adjuvant is administered at a dose of about 100×10^6 mesenchymal stem cells.
Infusion or direct injection route for the adjuvant
The adjuvant is administered by infusion or direct injection.
No MHC matching prior to administering allogeneic MSCs
Human mesenchymal stem cells are obtained from a human donor, and no MHC matching of the donor to the subject is employed prior to administration.
Overall, the claims focus on selecting subjects with inflammaging and aging frailty, administering a vaccine with an adjuvant of isolated allogeneic human mesenchymal stem cells that have not been genetically manipulated, and using an adjuvant amount effective at reducing inflammaging. Coverage further narrows the concept with optional constraints for inactivated-virus vaccines, biomarker reduction of intracellular TNF-α in B cells, specified MSC dosing, specified adjuvant administration route, and donor handling without MHC matching.
Stated Advantages
Enhancing a subject’s immune response to a vaccine.
Inducing an immune response in a subject whose immune system did not previously react to the vaccine.
Reducing inflammaging.
Decreasing intracellular TNF-α expression in B cells by at least two-fold.
Reducing intracellular TNF-α expression in B cells associated with the described immune response effects.
Documented Applications
Phase I/II HERA trial framework assessing improved adaptive immunity to influenza vaccine in aging frailty.
Administration of an influenza vaccine, including Fluzone High-Dose influenza vaccine, in an aging frailty context as described.
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