Evidence map›Paper›PMID 38819987›Full record

ArticleCell reports2024

Cholesterol reduction by immunization with a PCSK9 mimic.

Baoshan Zhang, Gwo-Yu Chuang, Andrea Biju, Daniel Biner, Jiaxuan Cheng, Yiran Wang, Saran Bao, Cara W Chao, Haotian Lei, Tracy Liu and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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

27 authors.

Baoshan ZhangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Gwo-Yu ChuangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Andrea BijuVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Daniel BinerVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Jiaxuan ChengVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Yiran WangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Saran BaoVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Cara W ChaoVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Haotian LeiResearch Technologies Branch, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Tracy LiuVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Alexandra F NazzariVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Yongping YangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Tongqing ZhouVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Steven J ChenVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Xuejun ChenVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Wing-Pui KongVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Li OuVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Danealle K ParchmentVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Edward K SarfoVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
HaoMin SiMaVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
John-Paul ToddVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Shuishu WangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Ruth A WoodwardVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Cheng ChengVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Reda RawiVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
John R MascolaVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA.
Peter D KwongVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.

Funding

Design Of ImmunogensZIAAI005024 · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2025 to 2025
$1.2M
Rational Immunogen Design Using Computational MethodsZICAI005114 · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2025 to 2025
$231k
Intramural NIH HHS ZIA AI005024NIGMS NIH HHS P41 GM103310
6 · The paper itself

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a plasma protein that controls cholesterol homeostasis. Here, we design a human PCSK9 mimic, named HIT01, with no consecutive 9-residue stretch in common with any human protein as a potential heart attack vaccine. Murine immunizations with HIT01 reduce low-density lipoprotein (LDL) and cholesterol levels by 40% and 30%, respectively. Immunization of cynomolgus macaques with HIT01-K21Q-R218E, a cleavage-resistant variant, elicits high-titer PCSK9-directed antibody responses and significantly reduces serum levels of cholesterol 2 weeks after each immunization. However, HIT01-K21Q-R218E immunizations also increase serum PCSK9 levels by up to 5-fold, likely due to PCSK9-binding antibodies altering the half-life of PCSK9. While vaccination with a PCSK9 mimic can induce antibodies that block interactions of PCSK9 with the LDL receptor, PCSK9-binding antibodies appear to alter homeostatic levels of PCSK9, thereby confounding its vaccine impact. Our results nevertheless suggest a mechanism for increasing the half-life of soluble regulatory factors by vaccination.

Indexed as

CholesterolImmunizationMacaca fascicularisProprotein Convertase 9AnimalsFemaleHumansMiceMice, Inbred C57BLReceptors, LDLCholesterolPCSK9 protein, humanProprotein Convertase 9Receptors, LDLcholesterolCP: ImmunologyCP: Metabolismhalf-lifeimmunogen designlow-density lipoproteinPCSK9proprotein convertase subtilisin/kexin type 9vaccine

Identifiers

PMID38819987
PMCPMC11305080

What Socratic 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 Socratic graph.