Evidence map›Paper›PMID 32080235›Full record

ArticleScientific reports2020

Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen.

Li Ou, Wing-Pui Kong, Gwo-Yu Chuang, Mridul Ghosh, Krishana Gulla, Sijy O'Dell, Joseph Varriale, Nathan Barefoot, Anita Changela, Cara W Chao and 25 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 56 citations in OpenAlex.

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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

35 authors at 5 institutions in 1 country.

Li Ou *Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Wing-Pui Kong *Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Mridul GhoshVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Krishana GullaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Sijy O'DellVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Joseph VarrialeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Nathan BarefootVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Anita ChangelaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Cara W ChaoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Cheng ChengVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Aliaksandr DruzVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Rui KongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Krisha McKeeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Reda RawiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Edward K SarfoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Arne SchönDepartment of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
Andrew ShaddeauVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Yaroslav TsybovskyElectron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA.
Raffaello VerardiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Shuishu WangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Timothy G WanningerVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Kai XuVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Gengcheng J YangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Yaqiu ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
VRC Production Program
Frank J ArnoldVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Nicole A Doria-RoseVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Q Paula LeiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Edward T RyanMassachusetts General Hospital, Boston, 02114, MA, USA.
Willie F VannCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, 20993, MD, USA.
John R MascolaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
Peter D KwongVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA. pdkwong@nih.gov.
National Institutes of Health · USCenter for Biologics Evaluation and Research · USJohns Hopkins University · USLeidos (United States) · USNational Institute of Allergy and Infectious Diseases · US

Funding

Design Of ImmunogensZIAAI005024 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$21.5M
HIV/AIDS Vaccine and Antibody DevelopmentZICAI005002 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHENG, CHENG · 2019 to 2025
$17.6M
Quantitative Immunological Assays to Assess HIV Antibodies and VaccinesZICAI005010 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PIERSON, THEODORE · 2019 to 2025
$5.6M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.3M
O-Specific Polysaccharide Responses and CholeraR01AI106878 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RYAN, EDWARD T. · 2014 to 2018
$3.7M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENIAID NIH HHS R01 AI106878
6 · The paper itself

Abstract

The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) - when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) - to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge. Here we report the preclinical development of recombinant tetanus toxoid heavy chain fragment (rTTHC) linked to FP8 (FP8-rTTHC) as a suitable FP-conjugate vaccine immunogen. We assessed 16 conjugates, made by coupling the 4 most prevalent FP8 sequences with 4 carrier proteins: the aforementioned KLH and rTTHC; the H. influenzae protein D (HiD); and the cross-reactive material from diphtheria toxin (CRM197). While each of the 16 FP8-carrier conjugates could elicit HIV-1-neutralizing responses, rTTHC conjugates induced higher FP-directed responses overall. A Sulfo-SIAB linker yielded superior results over an SM(PEG)2 linker but combinations of carriers, conjugation ratio of peptide to carrier, or choice of adjuvant (Adjuplex or Alum) did not significantly impact elicited FP-directed neutralizing responses in mice. Overall, SIAB-linked FP8-rTTHC appears to be a promising vaccine candidate for advancing to clinical assessment.

Indexed as

Adjuvants, ImmunologicAIDS VaccinesAmino Acid SequenceAnimalsCross ReactionsFemaleHIV-1ImmunizationMice, Inbred BALB CMice, Inbred C57BLNeutralization TestsPeptidesRecombinant Fusion ProteinsAdjuvants, ImmunologicAIDS VaccinesPeptidesRecombinant Fusion Proteins

Identifiers

PMID32080235
PMCPMC7033230
OpenAlexW3007220414

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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.