Evidence map›Paper›PMID 21801778›Full record

ArticleVaccine2011

Development of an interferon-gamma ELISPOT assay to detect human T cell responses to HSV-2.

Christine M Posavad, Amalia S Magaret, Lin Zhao, Dawn E Mueller, Anna Wald, Lawrence Corey

Abstract read
In one paragraph

Article in Vaccine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 13 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

6 authors at 2 institutions in 2 countries.

Christine M PosavadVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. posavad@uw.edu
Amalia S Magaret
Lin Zhao
Dawn E Mueller
Anna Wald
Lawrence Corey
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

THE PERINATAL COMPLICATIONS OF ASYMPTOMATIC GENITAL HERPES SIMPLEX VIRUSP01AI030731 · NIAID · UNIVERSITY OF WASHINGTON · PI MAGARET, AMALIA S. · 1991 to 2017
$34.3M
T Cell Immunity to HSV-2 in Immune Seronegative SubjectsR01AI091701 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI POSAVAD, CHRISTINE M · 2011 to 2015
$1.9M
Clinical Research in HSV InfectionsK24AI071113 · NIAID · UNIVERSITY OF WASHINGTON · PI WALD, ANNA · 2006 to 2015
$1.7M
Human Resistance to Herpes Simplex Virus InfectionsR01AI049394 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI POSAVAD, CHRISTINE M · 2002 to 2005
$1.2M
Innate Resistance to Mucosal HSV Infection in HumansR21AI083418 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI POSAVAD, CHRISTINE M · 2009 to 2010
$415k
HSV-SERONEGATIVE PERSONS WITH AQUIRED IMMUNITY TO HSVK22AI001776 · NIAID · UNIVERSITY OF WASHINGTON · PI POSAVAD, CHRISTINE M · 2001 to 2002
$269k
NIAID NIH HHS AI-030731NIAID NIH HHS AI-042428NIAID NIH HHS AI-049394NIAID NIH HHS AI-071113NIAID NIH HHS AI-083418NIAID NIH HHS K22 AI001776NIAID NIH HHS K24 AI071113NIAID NIH HHS P01 AI030731NIAID NIH HHS R01 AI049394NIAID NIH HHS R01 AI091701NIAID NIH HHS R21 AI083418
6 · The paper itself

Abstract

backgroundThe need for an HSV-2 vaccine is great considering the increasing prevalence of HSV-2 despite the widespread use of antiviral drugs. Human clinical trials of HSV-2 vaccines that elicit neutralizing antibodies have proven to be only partially effective suggesting that induction of effective T cell responses to HSV-2 is also a critical component to an efficacious vaccine. A sensitive and specific assay to measure HSV-specific T cell responses is a necessary part of vaccine development and thus we undertook the development of an interferon-γ (IFN-γ) ELISPOT assay to measure T cell responses to HSV-2.

methodsPBMC from HSV-seronegative (HSVneg) (n=35), HSV-1-seropositive (HSV-1+/2-) (n=20) and HSV-2-seropositive (HSV-2+) subjects (n=26) were screened by IFN-γ ELISPOT for T cell responses using 34 peptide pools representing 16 HSV-2 proteins including mostly virion and immediate-early (IE) proteins.

resultsOverall, 85% of HSV-2+ subjects had a positive response to the HSV-2 peptide pools and on average, HSV-2+ subjects responded to 3 peptide pools (range 1-10). The most frequent responses were to gD-2, UL39, UL46, ICP0, UL49, gB-2, and ICP4. In contrast, only 2 of 35 (6%) HSVneg subjects had detectable T cell responses and in both cases, responses were of low magnitude relative to responses in HSV-2+ subjects and were directed at a single peptide pool. The response rate to the HSV-2 peptide pools in HSV-1+/2- subjects was 40% suggesting that the HSV-2 peptide pools contain a significant number of type-common T cell epitopes. The IFN-γ ELISPOT assay detected CD4 and CD8 T cells directed at HSV-2 peptides as confirmed by intracellular cytokine staining and flow cytometry.

conclusionWe have developed a quantitative IFN-γ ELISPOT assay that detects both CD4 and CD8 T cells to HSV-2 peptides. This assay does not require large quantities of PBMC to generate dendritic cells for T cell stimulation, making it an ideal assay for monitoring the immunogenicity of candidate HSV-2 vaccines designed to elicit T cell responses to HSV-2 specific epitopes.

Indexed as

AdultCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunospot AssayEpitopes, T-LymphocyteFemaleHerpes Simplex Virus VaccinesHerpesvirus 1, HumanHerpesvirus 2, HumanHumansImmediate-Early ProteinsInterferon-gammaMaleMiddle AgedPeptidesPhenotypeEpitopes, T-LymphocyteHerpes Simplex Virus VaccinesImmediate-Early ProteinsInterferon-gammaPeptides

Identifiers

PMID21801778
PMCPMC3168963
OpenAlexW2053864860

What OpenQuestion holds

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LicenceTDM
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.