Evidence map›Paper›PMID 27702895›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination.

Hok Hei Tam, Mariane B Melo, Myungsun Kang, Jeisa M Pelet, Vera M Ruda, Maria H Foley, Joyce K Hu, Sudha Kumari, Jordan Crampton, Alexis D Baldeon and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 281 papers.

0numbers the graph read from it
0cells of the map it votes in
281citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

281 citing papers in PubMed, 415 citations in OpenAlex.

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221 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 2 countries.

Hok Hei TamDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-2358-0330
Mariane B MeloDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, & Harvard, Cambridge, MA 02139.ORCID 0000-0002-0409-2454
Myungsun KangDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
Jeisa M PeletDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Vera M RudaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Maria H FoleyDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Joyce K HuDivision of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037.
Sudha KumariDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, & Harvard, Cambridge, MA 02139.
Jordan CramptonDivision of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037.
Alexis D BaldeonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Rogier W SandersDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam-Zuidoost, The Netherlands.
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021.
Shane CrottyDivision of Vaccine Discovery, La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037.
Robert LangerDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
Daniel G AndersonDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139; djirvine@mit.edu dgander@mit.edu arupc@mit.edu.
Arup K ChakrabortyDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, & Harvard, Cambridge, MA 02139; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; djirvine@mit.edu dgander@mit.edu arupc@mit.edu.
Darrell J IrvineDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, & Harvard, Cambridge, MA 02139; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Howard Hughes Medical Institute, Chevy Chase, MD 20815 djirvine@mit.edu dgander@mit.edu arupc@mit.edu.
Massachusetts Institute of Technology · USRagon Institute of MGH, MIT and Harvard · USCornell University · USInternational AIDS Vaccine Initiative · USLa Jolla Institute for Immunology · US

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Maximizing germinal centers and somatic hypermutation to HIV Env immunogensR01AI125068 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI CROTTY, SHANE P, IRVINE, DARRELL J · 2016 to 2020
$4.3M
NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI125068NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.

Indexed as

Adjuvants, ImmunologicAIDS VaccinesAnimalsAntibodies, ViralAntibody AffinityB-LymphocytesCHO CellsCricetulusDrug Administration ScheduleFemaleGerminal CenterHEK293 CellsHIV Envelope Protein gp120HumansImmunogenicity, VaccineInfusion Pumps, ImplantableAdjuvants, ImmunologicAIDS VaccinesAntibodies, Viralgp120 protein, Human immunodeficiency virus 1HIV Envelope Protein gp120Lipid Amonophosphoryl lipid ARecombinant Fusion Proteinsantigen retentioncomputational immunologygerminal center formationhumoral responsevaccination kinetics

Identifiers

PMID27702895
PMCPMC5086995
OpenAlexW2527863850

What OpenQuestion holds

Textmetadata
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.