Evidence map›Paper›PMID 39632208›Full record

ArticleVaccine2025

Immune profile diversity is achieved with synthetic TLR4 agonists combined with the RG1-VLP vaccine in mice.

Rebecca L Matthews, Nazneen Khan, Bradley Beckman, Simran Sharma, Zackary Dietz, William D Picking, Grant Izmirlian, Chelsea Sanders, Stacy M Stocks, Simone Difilippantonio and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Vaccine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

16 authors.

Rebecca L MatthewsCancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Nazneen KhanCancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Bradley BeckmanCancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Simran SharmaDepartment of Veterinary Pathobiology and Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
Zackary DietzDepartment of Veterinary Pathobiology and Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
William D PickingDepartment of Veterinary Pathobiology and Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
Grant IzmirlianBiometry Research Group, Division of Cancer Prevention, NCI, Bethesda, MD, USA.
Chelsea SandersLaboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Stacy M StocksLaboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Simone DifilippantonioLaboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Reinhard KirnbauerLaboratory of Viral Oncology (LVO), Department of Dermatology, Medical University of Vienna, Austria.
Richard B RodenDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Ligia A PintoVaccine, Immunity, and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Robert H ShoemakerChemopreventive Agent Development Research Group, Division of Cancer Prevention, NCI, Bethesda, MD, USA.
Robert K ErnstDepartment of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA.
Jason D MarshallCancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. Electronic address: jason.marshall2@nih.gov.

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI WARNER KING HUH, TZYY-CHOOU WU · 2003 to 2026
$53.5M
Mouse modeling of HPV infectionR01CA233486 · NCI · JOHNS HOPKINS UNIVERSITY · PI HUNG, CHIEN-FU, RODEN, RICHARD BRUCE · 2019 to 2023
$3.0M
Development of Novel Spontaneous HPV Cervicovaginal Carcinoma Models for Cancer ImmunotherapyR01CA237067 · NCI · JOHNS HOPKINS UNIVERSITY · PI WU, TZYY-CHOOU · 2019 to 2023
$2.9M
Intramural NIH HHS Z99 CA999999NCI NIH HHS 75N91019D00024NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA098252NCI NIH HHS R01 CA233486NCI NIH HHS R01 CA237067NIAID NIH HHS HHSN272201800043C
6 · The paper itself

Abstract

The TLR4 (Toll-like receptor 4)-activating agonist MPLA (monophosphoryl lipid A) is a key component of the adjuvant systems AS01 and AS04, utilized in marketed preventive vaccines for several infectious pathogens. As MPLA is a biologically-derived product containing a mixture of several lipid A congeners with a 4' phosphoryl group and varying numbers of acyl chains with distinct activities, extensive efforts to refine its production and immunogenicity are ongoing; notably, the development of the BECC (Bacterial Enzymatic Combinatorial Chemistry) system in which bacteria express lipid A-modifying enzymes to produce a panoply of lipid A congeners. In an effort to characterize the adjuvant activity of these lipid A congeners, we compared biologically-derived and synthetic versions of BECC470 and BECC438 for adjuvant activity in BALB/c mice vaccinated with the HPV (Human papilloma virus) VLP-based vaccine, RG1-VLP. Synthetic BECC compounds compared favorably to biological versions and, in the case of synthetic BECC470, were routinely superior to their biologically-derived BECC counterpart. Synthetic BECC470-adjuvanted vaccines achieved broad spectrum immune activity characterized by elevated levels of total IgG and IgG2a subtype specific to HPV16 L1 VLPs and the HPV16 L2 peptide, as well as robust HPV16-neutralizing antibody titers. In addition, synthetic BECC470 promoted strong T cell responses to HPV16 L1, increased memory B cell frequency, and increased the T follicular helper cell (Tfh) population in draining lymph nodes. In contrast, the biologically-derived form of BECC470 induced an immune profile specific for highest levels of HPV16 L2-specific IgG2a as well as antibodies cross-neutralizing to HPV18 and HPV39. These data confirm that a synthetically-derived BECC compound can be combined with Alhydrogel to adjuvant the RG1-VLP vaccine as can biologically-derived BECC compounds and MPLA, albeit with subtly distinct immune responses. The distinctions in immune profiles triggered by these BECC compounds warrant further exploration for their capacity to activate TLR4 and modulate immune responses to vaccines.

Indexed as

Adjuvants, ImmunologicLipid AMice, Inbred BALB CToll-Like Receptor 4Adjuvants, VaccineAnimalsAntibodies, NeutralizingAntibodies, ViralFemaleMicePapillomavirus VaccinesVaccines, Virus-Like ParticleAdjuvants, ImmunologicAdjuvants, VaccineAntibodies, NeutralizingAntibodies, ViralLipid Amonophosphoryl lipid APapillomavirus VaccinesTlr4 protein, mouseToll-Like Receptor 4Vaccines, Virus-Like ParticleAdjuvantsHPVMouse modelNeutralizing antibodyProphylactic vaccineTLR4

Identifiers

PMID39632208
PMCPMC11655249

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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.