Evidence map›Paper›PMID 29799015›Full record

ArticleScientific reports2018

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity.

A A Latanova, S Petkov, A Kilpelainen, J Jansons, O E Latyshev, Y V Kuzmenko, J Hinkula, M A Abakumov, V T Valuev-Elliston, M Gomelsky and 6 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

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  9. Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action.Current topics in microbiology and immunology · 2022
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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

16 authors at 8 institutions in 4 countries.

A A LatanovaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. aalatanova@gmail.com.ORCID 0000-0002-2260-6551
S PetkovDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
A KilpelainenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
J JansonsRiga Stradins University, Riga, Latvia.
O E LatyshevGamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia.
Y V KuzmenkoEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
J HinkulaDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
M A AbakumovResearch and Education Center for Medical Nanobiotechnology, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia.
V T Valuev-EllistonEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
M GomelskyDepartment of Molecular Biology, University of Wyoming, Laramie, WY, 82071, USA.
V L KarpovEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
F ChiodiDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
B WahrenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
D Y LogunovGamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia.
E S StarodubovaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
M G IsaguliantsGamaleja Research Center of Epidemiology and Microbiology, Moscow, Russia. maria.issagouliantis@rsu.lv.
Engelhardt Institute of Molecular Biology · RUKarolinska Institutet · SERussian Academy of Sciences · RUGamalei Institute of Epidemiology and Microbiology · RULinköping University · SENational University of Science and Technology · RURiga Stradiņš University · LVUniversity of Wyoming · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid ("surrogate challenge"). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-γ production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T-cells, targeted epitopes at aa 199-220 and aa 528-543. Drug-resistance mutations disrupted the epitope at aa 205-220, while the CTL epitope at aa 202-210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.

Indexed as

AIDS VaccinesDrug Resistance, ViralVaccines, DNAAnimalsCalibrationCells, CulturedCodonDrug Delivery SystemsEpitopesHeLa CellsHIV-1HIV InfectionsHIV Reverse TranscriptaseHumansImmune EvasionImmunization, SecondaryAIDS VaccinesCodonEpitopesHIV Reverse Transcriptasereverse transcriptase, Human immunodeficiency virus 1Vaccines, DNA

Identifiers

PMID29799015
PMCPMC5967322
OpenAlexW2803662744

What OpenQuestion holds

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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.