Evidence map›Paper›PMID 27487086›Full record

ArticlePLoS pathogens2016

Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of Autologous Tier 2 Neutralizing Antibodies.

Yu Feng, Karen Tran, Shridhar Bale, Shailendra Kumar, Javier Guenaga, Richard Wilson, Natalia de Val, Heather Arendt, Joanne DeStefano, Andrew B Ward and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.4field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 74 citations in OpenAlex.

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  18. Review
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  20. Innovations in HIV-1 Vaccine Design.Clinical therapeutics · 2020
    Review
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

11 authors at 2 institutions in 1 country.

Yu FengIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.ORCID 0000-0003-1564-4098
Karen TranIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
Shridhar BaleDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
Shailendra KumarIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
Javier GuenagaIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
Richard WilsonIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
Natalia de ValDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Heather ArendtIAVI Design and Development Lab, Department of Research and Development, International AIDS Vaccine Initiative, Brooklyn, New York, United States of America.
Joanne DeStefanoIAVI Design and Development Lab, Department of Research and Development, International AIDS Vaccine Initiative, Brooklyn, New York, United States of America.
Andrew B WardIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
Richard T WyattIAVI Neutralizing Center at TSRI, Department of Research and Development, International AIDS Vaccine Initiative, La Jolla, California, United States of America.
International AIDS Vaccine Initiative · USScripps Research Institute · US

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Non-Human PrimatesP01AI104722 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WYATT, RICHARD THOMAS · 2014 to 2018
$14.6M
NIAID NIH HHS P01 AI104722NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

In the context of HIV vaccine design and development, HIV-1 spike mimetics displaying a range of stabilities were evaluated to determine whether more stable, well-ordered trimers would more efficiently elicit neutralizing antibodies. To begin, in vitro analysis of trimers derived from the cysteine-stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were evaluated. These native-like trimers, derived from HIV subtypes A, B, and C, displayed a range of thermostabilities, and were "stress-tested" at varying temperatures as a prelude to in vivo immunogenicity. Analysis was performed both in the absence and in the presence of two different adjuvants. Since partial trimer degradation was detected at 37°C before or after formulation with adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing) of the well-ordered trimers with glutaraldehyde increased overall thermostability, maintenance of well-ordered trimer integrity without or with adjuvant, and increased resistance to solid phase-associated trimer unfolding. Immunization of unfixed and fixed well-ordered trimers into animals revealed that the elicited tier 2 autologous neutralizing activity correlated with overall trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also led to higher tier 2 autologous neutralization titers. These results link retention of trimer quaternary packing with elicitation of tier 2 autologous neutralizing activity, providing important insights for HIV-1 vaccine design.

Indexed as

AIDS VaccinesAnimalsAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusGlutaralGuinea PigsHIV-1HIV AntibodiesHumansImmunogenicity, VaccineProtein MultimerizationProtein StabilityAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusGlutaralHIV Antibodies

Identifiers

PMID27487086
PMCPMC4972253
OpenAlexW2495414843

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.