Evidence map›Paper›PMID 19470949›Full record

ArticleJournal of the National Cancer Institute2009

Concatenated multitype L2 fusion proteins as candidate prophylactic pan-human papillomavirus vaccines.

Subhashini Jagu, Balasubramanyam Karanam, Ratish Gambhira, Sudha V Chivukula, Revathi J Chaganti, Douglas R Lowy, John T Schiller, Richard B S Roden

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of the National Cancer Institute, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
10.0field-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

100 citing papers in PubMed, 163 citations in OpenAlex.

  1. Review
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  6. Viral vector-based therapeutic HPV vaccines.Clinical and experimental medicine · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Review
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  13. Vaccination Strategies for the Control and Treatment of HPV Infection and HPV-Associated Cancer.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2021
    Article
  14. Review
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  16. Article
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40 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

8 authors at 2 institutions in 1 country.

Subhashini JaguDepartment of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.
Balasubramanyam Karanam
Ratish Gambhira
Sudha V Chivukula
Revathi J Chaganti
Douglas R Lowy
John T Schiller
Richard B S Roden
Johns Hopkins University · USNational Institutes of Health · US

Funding

Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI Richard Bruce Roden · 2003 to 2026
$53.5M
Understanding Papillomavirus Virion Proteins and VaccinesZIABC009052 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHILLER, JOHN T. · 2009 to 2025
$38.4M
Papillomavirus Virion Proteins and VaccinesZIABC010579 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LOWY, DOUGLAS R. · 2009 to 2025
$15.4M
Mechanisms of Papillomavirus NeutralizationR01CA118790 · NCI · JOHNS HOPKINS UNIVERSITY · PI RODEN, RICHARD BRUCE · 2007 to 2018
$2.9M
NCI NIH HHS CA118790NCI NIH HHS P50 CA098252
6 · The paper itself

Abstract

backgroundVaccination with minor capsid protein L2 induces antibodies that cross-neutralize diverse papillomavirus types. However, neutralizing antibody titers against the papillomavirus type from which the L2 vaccine was derived are generally higher than the titers against heterologous types, which could limit effectiveness against heterologous types. We hypothesized that vaccination with concatenated multitype L2 fusion proteins derived from known cross-protective epitopes of several divergent human papillomavirus (HPV) types might enhance immunity across clinically relevant HPV genotypes.

methodsAntibody responses of mice (n = 120) and rabbits (n = 23) to vaccination with HPV-16 amino-terminal L2 polypeptides or multitype L2 fusion proteins, namely, 11-200 x 3 (HPV types 6, 16, 18), 11-88 x 5 (HPV types 1, 5, 6, 16, 18), or 17-36 x 22 (five cutaneous, two mucosal low-risk, and 15 oncogenic types), that were formulated alone or in GPI-0100, alum, or 1018 ISS adjuvants were compared with vaccination with L1 virus-like particles (VLPs), including Gardasil, a licensed quadrivalent HPV L1 vaccine, and a negative control. Mice were challenged with HPV-16 pseudovirions 4 months after vaccination. Statistical tests were two-sided.

resultsThe HPV-16 L2 polypeptides generated robust HPV-16-neutralizing antibody responses, albeit lower than those to HPV-16 L1 VLPs, and lower responses against other HPVs. In contrast, vaccination with the multitype L2 fusion proteins 11-200 x 3 and 11-88 x 5 induced high serum neutralizing antibody titers against all heterologous HPVs tested. 11-200 x 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, P < .001) 4 months after vaccination as well as HPV-16 L1 VLPs, but 11-200 x 3 alone or formulated with either alum or 1018 ISS was less effective (reduction in HPV-16 infection, P < .001).

conclusionConcatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines.

Indexed as

Neutralization TestsAnalysis of VarianceAnimalsAntibodies, ViralB-LymphocytesCapsid ProteinsEnzyme-Linked Immunosorbent AssayEpitopesFemaleHuman papillomavirus 16Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18HumansImmune SeraMiceMice, Inbred BALB COncogene Proteins, ViralAntibodies, ViralCapsid ProteinsEpitopesHuman Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18Immune SeraL2 protein, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus Vaccines

Identifiers

PMID19470949
PMCPMC2689872
OpenAlexW2125726678

What OpenQuestion holds

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LicenceCC BY-NC
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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.