Primary mesenchymal stem cells as a vaccine platform

• US 10,472,647 B2
• Filed: 11/15/2013
• Issued: 11/12/2019
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY)
• Original Assignee: Administrators Of The Tulane Educational Fund (ADMINISTRATORS|DAVID H. COY)
• Inventors: Tomchuck, Suzanne L., Norton, Elizabeth B., Garry, Robert F., Bunnell, Bruce, Clements, John D.
• Primary Examiner(s): Ton, Thaian N
• Assistant Examiner(s): Montanari, David A.
• Application Number:
  US14/081,740
• Publication Number:
  US 20140178422A1
• Time in Patent Office: 2,188 Days
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/461 characterised by the cell type used
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Episomally transfected primary mesenchymal stem cells (MSC) express a polypeptide consisting of an antigenic polypeptide (e.g., one or more polypeptides) relating to a pathogen (e.g., one or more virus, bacterium, or parasite). The antigenic polypeptide can have the amino acid sequence of a natural polypeptide from the pathogen or an amino acid sequence differing from the natural sequence by one or more conservative amino acid substitutions. Uses and method for treating or preventing infections with episomally transfected primary MSC also are described.

Claims

1. Episomally transfected primary mesenchymal stems cells (ETP-MSC) which episomally and transiently express at least one polypeptide having a sequence of a natural antigen from a pathogenic organism, or having a sequence that differs from the natural antigen by one or more conservative amino acid substitutions and sharing at least 50% sequence identity with the sequence of the natural antigen;

and wherein the ETP-MSC elicit an antibody response to the antigen when the ETP-MSC are administered to a subject.

2. The ETP-MSC of claim 1 wherein the ETP-MSC episomally express a plurality of the antigens.

3. The ETP-MSC of claim 1 wherein the ETP-MSC episomally express about 2 to about 500 of the antigens.

4. The ETP-MSC of claim 1 wherein the ETP-MSC episomally express antigens from a plurality of pathogens.

5. The ETP-MSC of claim 1 wherein the antigen is a polypeptide from a virus.

6. The ETP-MSC of claim 1 wherein the MSC do not express an immune regulatory or costimulatory molecule.

7. The ETP-MSC of claim 1 wherein the antigen comprises HIV-1 gp120.

8. The ETP-MSC of claim 1 wherein the antigen is a polypeptide from a virus selected from the group consisting of:

adenoviruses;

papillomaviruses;

hepadnaviruses;

parvoviruses;

pox viruses;

Epstein-Barr virus;

cytomegalovirus (CMV);

herpes simplex viruses;

roseolovirus;

varicella zoster virus;

filoviruses;

paramyxoviruses;

orthomyxoviruses;

rhabdoviruses;

arenaviruses;

coronaviruses;

human enteroviruses;

hepatitis A virus;

human rhinoviruses;

polio virus;

retroviruses;

rotaviruses;

flaviviruses;

hepaciviruses; and

rubella virus.

9. A pharmaceutical composition comprising the ETP-MSC of claim 1 in a pharmaceutically acceptable carrier.