COMPOSITIONS COMPRISING BACTERIAL STRAINS
The invention provides compositions comprising bacterial strains for use as a vaccine adjuvant; for use in treating, preventing or delaying immunosenescence; or for use in enhancing a cell therapy, such as CAR-T. The invention also provides vaccine compositions comprising bacterial strains and one or more antigens.
1 .- 27 . (canceled)
28 . A method of treating, preventing, or delaying the progression of a disease or a condition associated with immunosenescence in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a bacterial strain of the genus Parabacteroides and a pharmaceutically acceptable excipient, diluent, or carrier, wherein the bacterial strain comprises a 16s rRNA gene sequence that has at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12, 13, 15, 16, 17, 18, or 19.
29 . The method of claim 28 , wherein the immunosenescence is characterized by a decrease in the number of B cells.
30 . The method of claim 28 , wherein the administering increases the number of B cells.
31 . The method of claim 30 , wherein the B cells comprise CD19+CD3−B cells.
32 . The method of claim 28 , wherein the disease or the condition associated with immunosenescence comprises a cardiovascular disease, a neurodegenerative disease, a cancer, type 2 diabetes, or an autoimmune disease.
33 . The method of claim 32 , wherein the neurodegenerative disease comprises Alzheimer's disease or Parkinson's disease.
34 . The method of claim 28 , wherein the composition is formulated for oral administration.
35 . The method of claim 28 , wherein the bacterial strain is lyophilized.
36 . The method of claim 28 , wherein the therapeutically effective amount comprises from about 1×10 3 to about 1×10 11 colony forming units per gram (CFU/g) with respect to the weight of the pharmaceutical composition.
37 . The method of claim 28 , wherein the bacterial strain comprises a bacterial strain of the species Parabacteroides distasonis, Parabacteroides goldsteinii , or Parabacteroides merdae.
38 . The method of claim 28 , wherein the bacterial strain comprises a 16s rRNA gene sequence that has at least 97% sequence identity to SEQ ID NO: 9, 10, 11, 12, 13, 16, 17, 18, or 19.
39 . The method of claim 28 , wherein the bacterial strain comprises a 16s rRNA gene sequence that has at least 98% sequence identity to SEQ ID NO: 9, 10, 11, 12, 13, 15, 16, 17, 18, or 19.
40 . The method of claim 28 , wherein the bacterial strain comprises a 16s rRNA gene sequence represented by SEQ ID NO: 9, 10, 11, 12, 13, 15, 16, 17, 18, or 19.
41 . The method of claim 28 , wherein the bacterial strain is the bacterial strain deposited under accession number 42382 at NCIMB.
42 . A method of enhancing an immune response against an antigen in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a bacterial strain of the genus Parabacteroides and a pharmaceutically acceptable excipient, diluent, or carrier, wherein the bacterial strain comprises a 16s rRNA gene sequence that has at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12, 13, 15, 16, 17, 18, or 19.
43 . The method of claim 42 , wherein the administering increases the expression level and/or activity of one or more of MCP-1, IL-5, CXCL1, IP-10, RANTES, MIP-1α, MIP-1β, MIP-2, GM-CSF and TNFα.
44 . The method of claim 42 , wherein the antigen comprises a pathogen antigen, a neoantigen, a glycoprotein antigen, an archaea antigen, or a tumor antigen.
45 . The method of claim 42 , wherein the pathogen antigen comprises a viral antigen, a bacterial antigen, a fungal antigen, or a parasite antigen.
46 . The method of claim 42 , wherein the bacterial strain comprises a 16s rRNA gene sequence that has at least 97% sequence identity to SEQ ID NO: 9, 10, 11, 12, 13, 15, 16, 17, 18, or 19.
47 . The method of claim 42 , wherein the bacterial strain is the bacterial strain deposited under accession number 42382 at NCIMB.