Synthetic antiserum for rapid-turnaround therapies

Patent metadata

Field	Value
Publication number	US-9920128-B2
Application number	US-201615001349-A
Country	US
Kind code	B2
Filing date	Jan 20, 2016
Priority date	Jan 28, 2015
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

A method for synthesizing an antiserum for rapid-turnaround therapies includes collecting antibody-secreting cells from a test subject, wherein the test subject has been exposed to a target biological agent and has produced an antibody response; selecting a subset of the antibody-secreting cells, the subset of the antibody-secreting cells producing antibodies that neutralize the target biological agent; generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent; tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identifiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells; analyzing antibody-type distribution in a natural immune response; synthesizing antibodies from the variable-region-coding DNA sequences to form synthetic antibodies; and mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural immune response to form the antiserum.

First claim

What is claimed is:

1. A method for synthesizing an antiserum for rapid-turnaround therapies, the method comprising:
collecting antibody-secreting cells from a test subject, wherein the test subject has been exposed to a target biological agent and has produced a successful antibody response;
selecting a subset of the antibody-secreting cells, the subset of the antibody-secreting cells producing antibodies that neutralize the target biological agent;
generating variable-region-coding DNA sequences from the antibodies that neutralize the target biological agent;
tagging amplicons of the variable-region-coding DNA sequences with unique nucleic acid identifiers to associate the variable-region-coding DNA sequences derived from individual ones of the subset of the antibody-secreting cells;
analyzing antibody-type distribution in a natural immune response;
synthesizing antibodies from the variable-region-coding DNA sequences to form synthetic antibodies; and
mixing the synthetic antibodies in a proportion equal to the antibody-type distribution in the natural immune response to form the antiserum.

2. The method according to claim 1 , wherein collecting the antibody-secreting cells from the test subject comprises:
extracting a sample containing white blood cells from blood or bone marrow of the test subject; and
isolating at least one of B cells or plasma cells from the sample.

3. The method according to claim 1 , wherein selecting the subset of the antibody-secreting cells comprises:
encapsulating each antibody-secreting cell in a droplet via droplet microfluidics;
screening each antibody-secreting cell for neutralization of the target biological agent via a binding assay within the droplet; and
selecting the subset of the antibody-secreting cells that neutralize the target biological agent.

4. The method according to claim 1 , further comprising an initial operation of priming the antibody response in the test subject.

5. The method according to claim 4 , wherein priming the antibody response in the test subject comprises vaccinating the test subject or selecting a previously infected test subject.

6. The method according to claim 5 , further comprising boosting the natural immune response in the test subject.

7. The method according to claim 4 , further comprising challenging the natural immune response in the test subject after priming the antibody response in the test subject and prior to collecting the antibody-secreting cells from the test subject.

8. The method according to claim 1 , further comprising validating neutralization properties of the antiserum after synthesis.

9. The method according to claim 1 , wherein the test subject comprises a human or a non-human animal.

10. The method according to claim 1 , wherein the target biological agent comprises at least one of a virus, a bacterium, a prion, a toxin, a cancer, or any combination thereof.

Assignees

• Univ Johns Hopkins

Inventors

• Lin Jeffrey S
• Feldman Andrew B
• Evans Jared D
• Wolfe Joshua T
• Weitz David
• Heyman John
• Pekosz Andrew S

Classifications

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K16/30 Primary

  from tumour cells · CPC title