Evidence map›Paper›PMID 30898066›Full record

ArticlemAbs2019

Antibody repertoire analysis of mouse immunization protocols using microfluidics and molecular genomics.

Michael A Asensio, Yoong Wearn Lim, Nicholas Wayham, Kacy Stadtmiller, Robert C Edgar, Jackson Leong, Renee Leong, Rena A Mizrahi, Matthew S Adams, Jan Fredrik Simons and 3 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Michael A Asensioa GigaGen Inc ., South San Francisco , CA , USA.
Yoong Wearn Lima GigaGen Inc ., South San Francisco , CA , USA.ORCID 0000-0002-8568-4901
Nicholas Wayhama GigaGen Inc ., South San Francisco , CA , USA.
Kacy Stadtmillera GigaGen Inc ., South San Francisco , CA , USA.
Robert C Edgara GigaGen Inc ., South San Francisco , CA , USA.
Jackson Leonga GigaGen Inc ., South San Francisco , CA , USA.
Renee Leonga GigaGen Inc ., South San Francisco , CA , USA.
Rena A Mizrahia GigaGen Inc ., South San Francisco , CA , USA.ORCID 0000-0001-8581-2240
Matthew S Adamsa GigaGen Inc ., South San Francisco , CA , USA.
Jan Fredrik Simonsa GigaGen Inc ., South San Francisco , CA , USA.
Matthew J Spindlera GigaGen Inc ., South San Francisco , CA , USA.
David S Johnsona GigaGen Inc ., South San Francisco , CA , USA.
Adam S Adlera GigaGen Inc ., South San Francisco , CA , USA.ORCID 0000-0001-9301-0037
GigaGen (United States) · US

Funding

Next-Generation Antibody Discovery and Development TechnologyR44CA187852 · NCI · GIGAGEN, INC. · PI JOHNSON, DAVID SCOTT · 2016 to 2018
$1.6M
NCI NIH HHS R44 CA187852
6 · The paper itself

Abstract

Immunization of mice followed by hybridoma or B-cell screening is one of the most common antibody discovery methods used to generate therapeutic monoclonal antibody (mAb) candidates. There are a multitude of different immunization protocols that can generate an immune response in animals. However, an extensive analysis of the antibody repertoires that these alternative immunization protocols can generate has not been performed. In this study, we immunized mice that transgenically express human antibodies with either programmed cell death 1 protein or cytotoxic T-lymphocyte associated protein 4 using four different immunization protocols, and then utilized a single cell microfluidic platform to generate tissue-specific, natively paired immunoglobulin (Ig) repertoires from each method and enriched for target-specific binders using yeast single-chain variable fragment (scFv) display. We deep sequenced the scFv repertoires from both the pre-sort and post-sort libraries. All methods and both targets yielded similar oligoclonality, variable (V) and joining (J) gene usage, and divergence from germline of enriched libraries. However, there were differences between targets and/or immunization protocols for overall clonal counts, complementarity-determining region 3 (CDR3) length, and antibody/CDR3 sequence diversity. Our data suggest that, although different immunization protocols may generate a response to an antigen, performing multiple immunization protocols in parallel can yield greater Ig diversity. We conclude that modern microfluidic methods, followed by an extensive molecular genomic analysis of antibody repertoires, can be used to quickly analyze new immunization protocols or mouse platforms.

Indexed as

Antibody DiversityAnimalsAntibodies, Monoclonal, HumanizedB-LymphocytesComplementarity Determining RegionsCTLA-4 AntigenGenomicsHigh-Throughput Nucleotide SequencingHumansHybridomasImmunizationMiceMice, TransgenicMicrofluidicsPeptide LibraryProgrammed Cell Death 1 ReceptorAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsCTLA-4 AntigenPeptide LibraryProgrammed Cell Death 1 ReceptorSingle-Chain AntibodiesadjuvantsCTLA-4deep sequencingHumanized mouse antibody repertoiresmouse immunizationPD-1yeast display

Identifiers

PMID30898066
PMCPMC6601537
OpenAlexW2924845790

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.