Evidence map›Paper›PMID 28778613›Full record

ArticleVaccine2017

Incorporation of RG1 epitope concatemers into a self-adjuvanting Flagellin-L2 vaccine broaden durable protection against cutaneous challenge with diverse human papillomavirus genotypes.

Kirill Kalnin, Sudha Chivukula, Timothy Tibbitts, Yanhua Yan, Svetlana Stegalkina, Lihua Shen, Jacqueline Cieszynski, Victor Costa, Robert Sabharwal, Stephen F Anderson and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Vaccine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
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  7. Prophylactic and Therapeutic HPV Vaccines: Current Scenario and Perspectives.Frontiers in cellular and infection microbiology · 2022
    Review
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  11. Article
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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

14 authors at 4 institutions in 2 countries.

Kirill KalninResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA. Electronic address: kirill.kalnin@sanofipasteur.com.
Sudha ChivukulaResearch, Sanofi Pasteur, Shantha, Hyderabad, AP, India.
Timothy TibbittsResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Yanhua YanResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Svetlana StegalkinaResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Lihua ShenResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Jacqueline CieszynskiResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Victor CostaResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Robert SabharwalResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Stephen F AndersonResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Neil ChristensenDepartment of Pathology, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Subhashini JaguDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Richard B S RodenDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Harry KleanthousResearch, Sanofi Pasteur, 38 Sidney Street, Cambridge, MA, USA.
Sanofi (United States) · USJohns Hopkins University · USPennsylvania State University · USSanofi (India) · IN

Funding

Mechanisms of Papillomavirus NeutralizationR01CA118790 · NCI · JOHNS HOPKINS UNIVERSITY · PI RODEN, RICHARD BRUCE · 2007 to 2018
$2.9M
NCI NIH HHS R01 CA118790
6 · The paper itself

Abstract

aimTo achieve durable and broad protection against human papillomaviruses by vaccination with multimers of minor capsid antigen L2 using self-adjuvanting fusions with the toll-like receptor-5 (TLR5) ligand bacterial flagellin (Fla) instead of co-formulation with alum.

methodsFla fusions with L2 protective epitopes comprising residues 11-200, 11-88 and/or 17-38 of a single or multiple HPV types were produced in E. coli and their capacity to activate TLR5 signaling was assessed. Immunogenicity was evaluated serially following administration of 3 intramuscular doses of Fla-L2 multimer without exogenous adjuvant, followed by challenge 1, 3, 6 or 12months later, and efficacy compared to vaccination with human doses of L1 VLP vaccines (Gardasil and Cervarix) or L2 multimer formulated in alum. Serum antibody responses were assessed by peptide ELISA, in vitro neutralization assays and passive transfer to naïve rabbits in which End-Point Protection Titers (EPPT) were determined using serial dilutions of pooled immune sera collected 1, 3, 6 or 12months after completing active immunization. Efficacy was assessed by determining wart volume following concurrent challenge at different sites with HPV6/16/18/31/45/58 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes.

resultsVaccination in the absence of exogenous adjuvant with Fla-HPV16 L2 11-200 fusion protein elicited durable protection against HPV16, but limited cross-protection against other HPV types. Peptide mapping data suggested the importance of the 17-38 aa region in conferring immunity. Indeed, addition of L2 residues 17-38 of HPV6/18/31/39/52 to a Fla-HPV16 L2 11-200 or 11-88 elicited broader protection via active or passive immunization, similar to that seen with vaccination with an alum-adjuvanted L2 multimer comprising the aa 11-88 peptides of five or eight genital HPV types.

conclusionsVaccination with flagellin fused L2 multimers provided lasting (>1year) immunity without the need for an exogenous adjuvant. Inclusion of the L2 amino acid 17-38 region in such multi-HPV type fusions expanded the spectrum of protection.

Indexed as

Adjuvants, ImmunologicAnimalsAntibodies, NeutralizingCapsid ProteinsEnzyme-Linked Immunosorbent AssayEpitopesFlagellinGenotypeHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus InfectionsPapillomavirus VaccinesRabbitsAdjuvants, ImmunologicAntibodies, NeutralizingCapsid ProteinsEpitopesFlagellinhuman papillomavirus vaccine, L1 type 16, 18L2 protein, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus VaccinesCutaneous challengeFlagellinHPVHuman papillomavirusL2Neutralizing antibodyProphylactic vaccineProtective efficacy

Identifiers

PMID28778613
PMCPMC6454882
OpenAlexW2740979648

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.