Evidence map›Paper›PMID 23536912›Full record

ArticlePloS one2013

Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

Kihyuck Kwak, Rosie Jiang, Subhashini Jagu, Joshua W Wang, Chenguang Wang, Neil D Christensen, Richard B S Roden

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 19 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

7 authors at 2 institutions in 1 country.

Kihyuck KwakDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Rosie Jiang
Subhashini Jagu
Joshua W Wang
Chenguang Wang
Neil D Christensen
Richard B S Roden
Johns Hopkins University · USPenn State Milton S. Hershey Medical Center · 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
Papillomavirus Host InterationR01CA047622 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI CHRISTENSEN, NEIL D · 1988 to 2015
$3.8M
Mechanisms of Papillomavirus NeutralizationR01CA118790 · NCI · JOHNS HOPKINS UNIVERSITY · PI RODEN, RICHARD BRUCE · 2007 to 2018
$2.9M
NCI NIH HHS CA118790NCI NIH HHS P50 CA098252NCI NIH HHS R01 CA047622NCI NIH HHS R01 CA118790
6 · The paper itself

Abstract

objectivesNaked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV) L1 and L2 DNA vaccination.

methodsBalb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8) or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.

resultsElectroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2) vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type. DISCUSSION: Multivalent vaccination via in vivo electroporation requires spatial separation of individual type L1 DNA vaccines.

Indexed as

ElectroporationAlphapapillomavirusAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody SpecificityCapsid ProteinsCell LineHuman Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18HumansMicePapillomavirus InfectionsPapillomavirus VaccinesVaccinationVaccines, DNAAntibodies, NeutralizingAntibodies, ViralCapsid ProteinsHuman Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18Papillomavirus VaccinesVaccines, DNA

Identifiers

PMID23536912
PMCPMC3607584
OpenAlexW2028907068

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.