Evidence map›Paper›PMID 26741406›Full record

ArticleNature protocols2016

In vitro reconstitution of B cell receptor-antigen interactions to evaluate potential vaccine candidates.

Grant C Weaver, Rina F Villar, Masaru Kanekiyo, Gary J Nabel, John R Mascola, Daniel Lingwood

Open access · greenAbstract read
In one paragraph

Article in Nature protocols, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

51 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. In the activation of HPV-specific human B cells HPV-VLP vaccines mimic membrane-associated antigens.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Learning the language of antibody hypervariability.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. The CH1 domain influences the expression and antigen sensing of the HIV-specific CH31 IgM-BCR and IgG-BCR.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  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

6 authors at 3 institutions in 1 country.

Grant C WeaverThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute for Technology and Harvard University, Cambridge, Massachusetts, USA.
Rina F VillarThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute for Technology and Harvard University, Cambridge, Massachusetts, USA.
Masaru KanekiyoVaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0001-5767-1532
Gary J NabelSanofi, Cambridge, Massachusetts, USA.
John R MascolaVaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Daniel LingwoodThe Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute for Technology and Harvard University, Cambridge, Massachusetts, USA.
Ragon Institute of MGH, MIT and Harvard · USNational Institutes of Health · USSanofi (United States) · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Defining and Exploiting a Genetic Template for an HIV VaccineDP2DA042422 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI LINGWOOD, DANIEL · 2016 to 2016
$2.6M
NIAID NIH HHS P30 AI060354NIDA NIH HHS DP2 DA042422
6 · The paper itself

Abstract

Predicting immune responses before vaccination is challenging because of the complexity of the governing parameters. Nevertheless, recent work has shown that B cell receptor (BCR)-antigen engagement in vitro can prove a powerful means of informing the design of antibody-based vaccines. We have developed this principle into a two-phased immunogen evaluation pipeline to rank-order vaccine candidates. In phase 1, recombinant antigens are screened for reactivity to the germline precursors that produce the antibody responses of interest. To both mimic the architecture of initial antigen engagement and facilitate rapid immunogen screening, these antibodies are expressed as membrane-anchored IgM (mIgM) in 293F indicator cells. In phase 2, the binding hits are multimerized by nanoparticle or proteoliposome display, and they are evaluated for BCR triggering in an engineered B cell line displaying the IgM sequences of interest. Key developments that complement existing methodology in this area include the following: (i) introduction of a high-throughput screening step before evaluation of more time-intensive BCR-triggering analyses; (ii) generalizable multivalent antigen-display platforms needed for BCR activation; and (iii) engineered use of a human B cell line that does not display endogenous antibody, but only ectopically expressed BCR sequences of interest. Through this pipeline, the capacity to initiate favorable antibody responses is evaluated. The entire protocol can be completed within 2.5 months.

Indexed as

AntigensB-LymphocytesCell LineHumansProtein BindingReceptors, Antigen, B-CellVaccinesAntigensReceptors, Antigen, B-CellVaccines

Identifiers

PMID26741406
PMCPMC6956844
OpenAlexW2256987374

What OpenQuestion holds

Textmetadata
LicenceTDM
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.