Evidence map›Paper›PMID 26251214›Full record

Trial reportHepatology (Baltimore, Md.)2015

Antibodies to an interfering epitope in hepatitis C virus E2 can mask vaccine-induced neutralizing activity.

Alla Kachko, Sharon E Frey, Lev Sirota, Ranjit Ray, Frances Wells, Iryna Zubkova, Pei Zhang, Marian E Major

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

20 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Emerging and Pandemic Pathogens: Lessons Learned From a Clinical Research Network.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Synergistic anti-HCV broadly neutralizing human monoclonal antibodies with independent mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Article
  20. 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

8 authors at 3 institutions in 1 country.

Alla KachkoDivision of Viral Products, CBER/FDA, Silver Spring, MD.
Sharon E FreyDivision of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St Louis, MO.
Lev SirotaDivision of Biostatistics, Office of Biostatistics and Epidemiology, CBER/FDA, Silver Spring, MD.
Ranjit RayDivision of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St Louis, MO.
Frances WellsDivision of Viral Products, CBER/FDA, Silver Spring, MD.
Iryna ZubkovaDivision of Viral Products, CBER/FDA, Silver Spring, MD.
Pei ZhangDivision of Hematology, CBER/FDA, Silver Spring, MD.
Marian E MajorDivision of Viral Products, CBER/FDA, Silver Spring, MD.
Global Viral · USSaint Louis University · USCancer Research And Biostatistics · US

Funding

EVALUATION OF CONTROL MEASURES AGAINST DISEASES OTHER THAN AIDS-266025464N01AI025464 · NIAID · SAINT LOUIS UNIVERSITY · PI CHAPLESKI, ELIZABETH · 2003 to 2006
–
Pathogenesis and prevention of hepatitis virus infectionZ01BK004010 · BK · PI MAJOR, MARIAN · 2003 to 2003
–
FDA HHS Z01 BK 04010-11NIAID NIH HHS N01 AI025464NIAID NIH HHS N01-AI-25464
6 · The paper itself

Abstract

unlabelledHepatitis C virus (HCV) neutralization occurring at the E2 region 412-426 (EP-I) could be enhanced when antibodies directed specifically to the E2 region 434-446 (EP-II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so-called antibody interference. Here, we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins. One hundred twelve blinded serum samples from a phase I, placebo-controlled, dose escalation trial using recombinant HCV E1E2 with MF59C.1 adjuvant in healthy HCV-negative adults were tested in enzyme-linked immunosorbent assay for binding reactivity to peptides representing the E2 regions 412-426 (EP-I) and 434-446 (EP-II). All samples were subsequently tested for neutralizing activity using cell-culture HCV 1a(H77)/2a chimera, HCV pseudotype particles (HCVpp) H77, and HCVpp HCV-1 after treatment to remove EP-II-specific antibodies or mock treatment with a control peptide. Among the 112 serum samples, we found 22 double positive (EP-I and EP-II), 6 EP-II positive only, 14 EP-I positive only, and 70 double negative. Depleting EP-II antibodies from double-positive serum samples increased 50% inhibitory dose (ID50) neutralizing antibody titers (up to 4.9-fold) in up to 72% of samples (P ≤ 0.0005), contrasting with ID50 neutralization titer increases in 2 of 70 double-negative samples (2.9%; P > 0.5). In addition, EP-I-specific antibody levels in serum samples showed a significant correlation with ID50 neutralization titers when EP-II antibodies were removed (P < 0.0003).

conclusionThese data show that antibodies to the region 434-446 are induced during immunization of individuals with recombinant E1E2 proteins, and that these antibodies can mask effective neutralizing activity from EP-I-specific antibodies. Elicitation of EP-II-specific antibodies with interfering capacity should be avoided in producing an effective cross-neutralizing vaccine aimed at the HCV envelope proteins.

Indexed as

AnimalsAntibodies, NeutralizingEpitopesHepacivirusHepatitis C AntibodiesHumansPan troglodytesViral Hepatitis VaccinesAntibodies, NeutralizingEpitopesHepatitis C AntibodiesViral Hepatitis Vaccines

Identifiers

PMID26251214
PMCPMC4681649
OpenAlexW1942705005

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.