IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine

James E. McLaren, Mathew Clement, Morgan Marsden, Kelly L. Miners, Sian Llewellyn-Lacey, Emma J. Grant, Anzelika Rubina, Silvia Gimeno Brias, Emma Gostick, Maria A. Stacey, Selinda J. Orr, Richard J. Stanton, Kristin Ladell, David A. Price, Ian R. Humphreys

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Candidate vaccines designed to generate T cell–based immunity are typically vectored by nonpersistent viruses, which largely fail to elicit durable effector memory T cell responses. This limitation can be overcome using recombinant strains of CMV. Proof-of-principle studies have demonstrated the potential benefits of this approach, most notably in the SIV model, but safety concerns require the development of nonreplicating alternatives with comparable immunogenicity. In this study, we show that IL-33 promotes the accumulation and recall kinetics of circulating and tissue-resident memory T cells in mice infected with murine CMV. Using a replication-deficient murine CMV vector, we further show that exogenous IL-33 boosts vaccine-induced memory T cell responses, which protect against subsequent heterologous viral challenge. These data suggest that IL-33 could serve as a useful adjuvant to improve the efficacy of vaccines based on attenuated derivatives of CMV. The Journal of Immunology, 2019, 202: 943–955.

Original languageEnglish
Pages (from-to)943-955
Number of pages13
JournalJournal of Immunology
Volume202
Issue number3
DOIs
Publication statusPublished - 1 Feb 2019

Cite this

McLaren, James E. ; Clement, Mathew ; Marsden, Morgan ; Miners, Kelly L. ; Llewellyn-Lacey, Sian ; Grant, Emma J. ; Rubina, Anzelika ; Gimeno Brias, Silvia ; Gostick, Emma ; Stacey, Maria A. ; Orr, Selinda J. ; Stanton, Richard J. ; Ladell, Kristin ; Price, David A. ; Humphreys, Ian R. / IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine. In: Journal of Immunology. 2019 ; Vol. 202, No. 3. pp. 943-955.
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title = "IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine",
abstract = "Candidate vaccines designed to generate T cell–based immunity are typically vectored by nonpersistent viruses, which largely fail to elicit durable effector memory T cell responses. This limitation can be overcome using recombinant strains of CMV. Proof-of-principle studies have demonstrated the potential benefits of this approach, most notably in the SIV model, but safety concerns require the development of nonreplicating alternatives with comparable immunogenicity. In this study, we show that IL-33 promotes the accumulation and recall kinetics of circulating and tissue-resident memory T cells in mice infected with murine CMV. Using a replication-deficient murine CMV vector, we further show that exogenous IL-33 boosts vaccine-induced memory T cell responses, which protect against subsequent heterologous viral challenge. These data suggest that IL-33 could serve as a useful adjuvant to improve the efficacy of vaccines based on attenuated derivatives of CMV. The Journal of Immunology, 2019, 202: 943–955.",
author = "McLaren, {James E.} and Mathew Clement and Morgan Marsden and Miners, {Kelly L.} and Sian Llewellyn-Lacey and Grant, {Emma J.} and Anzelika Rubina and {Gimeno Brias}, Silvia and Emma Gostick and Stacey, {Maria A.} and Orr, {Selinda J.} and Stanton, {Richard J.} and Kristin Ladell and Price, {David A.} and Humphreys, {Ian R.}",
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McLaren, JE, Clement, M, Marsden, M, Miners, KL, Llewellyn-Lacey, S, Grant, EJ, Rubina, A, Gimeno Brias, S, Gostick, E, Stacey, MA, Orr, SJ, Stanton, RJ, Ladell, K, Price, DA & Humphreys, IR 2019, 'IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine', Journal of Immunology, vol. 202, no. 3, pp. 943-955. https://doi.org/10.4049/jimmunol.1701757

IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine. / McLaren, James E.; Clement, Mathew; Marsden, Morgan; Miners, Kelly L.; Llewellyn-Lacey, Sian; Grant, Emma J.; Rubina, Anzelika; Gimeno Brias, Silvia; Gostick, Emma; Stacey, Maria A.; Orr, Selinda J.; Stanton, Richard J.; Ladell, Kristin; Price, David A.; Humphreys, Ian R.

In: Journal of Immunology, Vol. 202, No. 3, 01.02.2019, p. 943-955.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - IL-33 augments virus-specific memory T cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccine

AU - McLaren, James E.

AU - Clement, Mathew

AU - Marsden, Morgan

AU - Miners, Kelly L.

AU - Llewellyn-Lacey, Sian

AU - Grant, Emma J.

AU - Rubina, Anzelika

AU - Gimeno Brias, Silvia

AU - Gostick, Emma

AU - Stacey, Maria A.

AU - Orr, Selinda J.

AU - Stanton, Richard J.

AU - Ladell, Kristin

AU - Price, David A.

AU - Humphreys, Ian R.

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AB - Candidate vaccines designed to generate T cell–based immunity are typically vectored by nonpersistent viruses, which largely fail to elicit durable effector memory T cell responses. This limitation can be overcome using recombinant strains of CMV. Proof-of-principle studies have demonstrated the potential benefits of this approach, most notably in the SIV model, but safety concerns require the development of nonreplicating alternatives with comparable immunogenicity. In this study, we show that IL-33 promotes the accumulation and recall kinetics of circulating and tissue-resident memory T cells in mice infected with murine CMV. Using a replication-deficient murine CMV vector, we further show that exogenous IL-33 boosts vaccine-induced memory T cell responses, which protect against subsequent heterologous viral challenge. These data suggest that IL-33 could serve as a useful adjuvant to improve the efficacy of vaccines based on attenuated derivatives of CMV. The Journal of Immunology, 2019, 202: 943–955.

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SN - 0022-1767

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