Evidence map›Paper›PMID 35336946›Full record

ArticleViruses2022

Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.

Lauren M Hook, Sita Awasthi, Tina M Cairns, Mohamad-Gabriel Alameh, Bernard T Fowler, Kevin P Egan, Molly M H Sung, Drew Weissman, Gary H Cohen, Harvey M Friedman

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2022. 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
2.6field-weighted citation impact, top 10% 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, 17 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

10 authors at 2 institutions in 2 countries.

Lauren M HookInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-5540-2459
Sita AwasthiInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8230-3635
Tina M CairnsDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mohamad-Gabriel AlamehInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-5672-6930
Bernard T FowlerInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kevin P EganInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Molly M H SungAcuitas Therapeutics Inc., Vancouver, BC V6T 1Z3, Canada.ORCID 0000-0002-0874-0922
Drew WeissmanInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-1501-6510
Gary H CohenDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Harvey M FriedmanInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-0765-9460
University of Pennsylvania · USAcuitas Therapeutics (Canada) · CA

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Nucleoside-modified mRNA vaccine for prevention and treatment of genital herpesR01AI139618 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Harvey Michael Friedman · 2019 to 2026
$6.4M
NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI139618
6 · The paper itself

Abstract

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.

Indexed as

Herpes GenitalisVaccinesAnimalsAntibodies, NeutralizingAntibodies, ViralEpitopesHerpesvirus 2, HumanLiposomesMiceNanoparticlesRNA, MessengerViral Envelope ProteinsAntibodies, NeutralizingAntibodies, ViralEpitopesglycoprotein D-herpes simplex virus type 2Lipid NanoparticlesLiposomesRNA, MessengerVaccinesViral Envelope Proteinsepitope mappinggenital herpes vaccineglycoprotein Dherpes simplex virus type 2IgG ELISAlipid nanoparticleneutralizing antibodiesnucleoside-modified mRNAsurface plasmon resonance

Identifiers

PMID35336946
PMCPMC8953786
OpenAlexW4220934545

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.