AUTOLOGOUS CELL BASED SARS-COV-2 VACCINES
Disclosed herein are multi-antigenic autologous, cell-based SARS-CoV-2 vaccines comprising autologous antigen presenting cells (APCs) displaying at least two different SARS-CoV-2 antigens. These vaccines can be used to prevent SARS-CoV-2 infection or COVID-19. Further disclosed are methods for producing and using the vaccines.
1 . A multi-antigenic autologous, cell-based SARS-CoV-2 vaccine, said vaccine comprising autologous antigen presenting cells (APCs) displaying at least two different SARS-CoV-2 antigens.
2 . The vaccine of claim 1 , wherein said APCs are activated, and wherein said APCs comprise dendritic cells, macrophages, B cells, monocytes or a combination thereof.
3 . The vaccine of claim 1 , wherein said at least two different SARS-CoV-2 antigens comprise SARS-CoV-2 structural protein antigens, and/or comprise antigens of the spike (S) protein, membrane (M) protein, nucleocapsid (N) protein, envelope (E) protein, any part thereof, or any combination thereof.
4 . (canceled)
5 . The vaccine of claim 3 , wherein said SARS-CoV-2 spike protein antigen comprises a S1 subunit, S2 subunit, or receptor binding domain (RBD) antigen.
6 . (canceled)
7 . (canceled)
8 . The vaccine of claim 1 , wherein said APCs have been contacted with mRNAs encoding SARS-CoV-2 antigens or said APCs have been contacted with a preparation of SARS-CoV-2 particles ex-vivo, wherein:
(a) the preparation of SARS-CoV-2 particles comprises chemically inactivated or attenuated live SARS-CoV-2 particles;
(b) the preparation of SARS-CoV-2 particles comprises at least two SARS-CoV-2 variants; or
(c) both (a) and (b).
9 . (canceled)
10 . (canceled)
11 . (canceled)
12 . (canceled)
13 . A pharmaceutical composition comprising the vaccine of claim 1 .
14 . A method for producing a multi-antigenic autologous, cell-based SARS-CoV-2 vaccine, comprising autologous antigen presenting cells (APCs) displaying at least two different SARS-CoV-2 antigens, said method comprising:
(a) obtaining a population of peripheral blood mononuclear cells (PBMCs) from a subject;
(b) isolating and culturing APCs from said population of PBMCs;
(c) contacting said APCs with a preparation of SARS-CoV-2 particles or with mRNAs encoding SARS-CoV-2 antigens for a time period sufficient to generate APCs displaying at least two different SARS-CoV-2 antigens; and
(d) optionally isolating and expanding said APCs from step (c).
15 . The method of claim 14 , wherein:
(a) the preparation of SARS-CoV-2 particles comprises chemically inactivated or attenuated live SARS-CoV-2 particles;
(b) the preparation of SARS-CoV-2 particles comprises at least two SARS-CoV-2 variants; or
(c) both (a) and (b).
16 . (canceled)
17 . The method of claim 14 , wherein said at least two different SARS-CoV-2 antigens comprise SARS-CoV-2 structural protein antigens, and/or comprise antigens of the spike (S) protein, membrane (M) protein, nucleocapsid (N) protein, envelope (E) protein, any part thereof, or any combination thereof.
18 . (canceled)
19 . The method of claim 17 , wherein said SARS-CoV-2 spike protein antigen comprises a S1 subunit, S2 subunit, or receptor binding domain (RBD) antigen.
20 . The method of claim 14 , wherein said SARS-CoV-2 particles are contacted at a multiplicity of infection (MOI) of between 0.001 and 10.
21 . (canceled)
22 . The method of claim 14 , wherein the APCs are contacted with a preparation of SARS-CoV-2 particles in the presence of a transduction reagent.
23 . The method of claim 22 , wherein said transduction reagent comprises polybrene (PB).
24 . The method of claim 14 , wherein said APCs comprise dendritic cells, macrophages, B cells, monocytes, or a combination thereof.
25 . (canceled)
26 . A method for preventing or treating a SARS-CoV-2 infection in a subject, the method comprising:
(a) obtaining a population of peripheral blood mononuclear cells (PBMCs) from a subject;
(b) isolating and culturing APCs from said population of PBMCs;
(c) contacting said APCs with a preparation of SARS-CoV-2 particles or with mRNAs encoding SARS-CoV-2 antigens for a time period sufficient to generate APCs displaying at least two different SARS-CoV-2 antigens;
(d) optionally isolating and expanding said APCs from step (c); and
(e) administering said APCs to said subject.
27 . The method of claim 26 , wherein:
(a) said preparation of SARS-CoV-2 particles comprises chemically inactivated or attenuated live SARS-CoV-2 particles;
(b) the preparation of SARS-CoV-2 particles comprises at least two SARS-CoV-2 variants; or
(c) both (a) and (b).
28 . (canceled)
29 . The method of claim 26 , wherein said at least two different SARS-CoV-2 antigens comprise SARS-CoV-2 structural protein antigens, and/or comprise antigens of the spike (S) protein, membrane (M) protein, nucleocapsid (N) protein, envelope (E) protein, any part thereof, or any combination thereof.
30 . (canceled)
31 . The method of claim 29 , wherein said SARS-CoV-2 spike protein antigen comprises a S1 subunit, S2 subunit, or receptor binding domain (RBD) antigen.
32 . The method of claim 26 , wherein said SARS-CoV-2 particles are contacted at a multiplicity of infection (MOI) of between 0.001 and 10.
33 . (canceled)
34 . The method of claim 26 , wherein said APCs comprise dendritic cells, macrophages, B cells, monocytes or a combination thereof.
35 . (canceled)
36 . (canceled)
37 . (canceled)