Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

Cunningham, Paula; Lloyd, Megan; Harvey, Naomi D.; Williams, Elizabeth L.; Hardy, Christopher M.; Redwood, Alec; Lawson, Malcolm; Shellam, Geoffrey

doi:10.1016/j.vaccine.2010.03.012

Cited by 5 publications

(7 citation statements)

References 41 publications

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“…1C, right panel), M38-specific T cells failed to inflate after infection by MCMV-GFP-SL8. These data mirrored our previous observations with a second strain of MCMV expressing OVA (K181-tfr-ova) [10], which expresses the full-length OVA protein [28].…”

Section: Siinfekl-specific Cd8 + T Cells Dominate Memory Inflation Afsupporting

confidence: 88%

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

et al. 2013

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Summary Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus-specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T cell receptors (TCR) with high affinity for HCMV-derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT-I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT-Is were selectively enriched during the first three weeks of infection. Similarly, in the absence of OT-Is, the functional avidity of SIINFEKL-specific T cells increased from early to late times post infection. However, even when exceedingly small numbers of OT-Is were transferred, their inflation limited the inflation of host-derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT-I T cells in some mice, which allowed host-derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.

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Section: Siinfekl-specific Cd8 + T Cells Dominate Memory Inflation Afsupporting

confidence: 88%

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

et al. 2013

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“…8F. MCMV-SL8-015 or MCMV-K181-trf-OVA (MCMV-OVA), have been previously described (34, 35), and were used in fig. 7, fig.…”

Section: Methodsmentioning

confidence: 99%

The Chemokine Receptor CXCR3 Promotes CD8+ T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection

Caldeira-Dantas

Furmanak

Smith

et al. 2018

The Journal of Immunology

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Recent work indicates that salivary glands are able to constitutively recruit CD8 T cells and retain them as tissue-resident memory T cells, independently of local infection, inflammation, or Ag. To understand the mechanisms supporting T cell recruitment to the salivary gland, we compared T cell migration to the salivary gland in mice that were infected or not with murine CMV (MCMV), a herpesvirus that infects the salivary gland and promotes the accumulation of salivary gland tissue-resident memory T cells. We found that acute MCMV infection increased rapid T cell recruitment to the salivary gland but that equal numbers of activated CD8 T cells eventually accumulated in infected and uninfected glands. T cell recruitment to uninfected salivary glands depended on chemokines and the integrin α Several chemokines were expressed in the salivary glands of infected and uninfected mice, and many of these could promote the migration of MCMV-specific T cells in vitro. MCMV infection increased the expression of chemokines that interact with the receptors CXCR3 and CCR5, but neither receptor was needed for T cell recruitment to the salivary gland during MCMV infection. Unexpectedly, however, the chemokine receptor CXCR3 was critical for T cell accumulation in uninfected salivary glands. Together, these data suggest that CXCR3 and the integrin α mediate T cell recruitment to uninfected salivary glands but that redundant mechanisms mediate T cell recruitment after MCMV infection.

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“…; Figure a) or intraperitoneal (i.p. ; Figure b) inoculation, as described for similar IE2 disruptions . The attenuation was less marked after i.p.…”

Section: Resultsmentioning

confidence: 62%

“…MCMV expressing OVA from its IE2 locus via an HCMV IE1 (Human Cytomegalovirus Immediate early gene 1) promoter (MCMV‐OVA) is described . We expressed membrane‐associated OVA (mOVA) the same way (MCMV‐mOVA; Figure a).…”

Section: Resultsmentioning

confidence: 99%

“…All MCMVs were derived from strain K181 (Perth). MCMV‐OVA, in which OVA is expressed from an HCMV IE1 promoter‐driven cassette inserted at the 5′ end of the IE2 locus (deleting its main transcription start site), is described . MCMV‐mOVA—using the same fusion protein as in MHV‐mOVA—was expressed from an HCMV IE1 promoter in the same way, and inserted between equivalent plasmid‐cloned MCMV genomic flanks, so as to insert it into the IE2 locus.…”

Section: Methodsmentioning

confidence: 99%

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Membrane association of a model CD4⁺ T‐cell vaccine antigen confers enhanced yet incomplete protection against murid herpesvirus‐4 infection

et al. 2020

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Vaccination against c-herpesviruses has proved difficult. CD4 + T cells are essential to contain infection, but how best to prime them and whether this can reduce viral loads remain unclear. To address these questions, we used ovalbumin (OVA) as a model antigen, delivering it with murine cytomegalovirus (MCMV) to protect mice against OVA-expressing murine herpesvirus-4 (MuHV-4). Membrane-associated OVA (mOVA) was more effective than soluble OVA, both to prime CD4 + T cells and as an effector target. It was also a better target than an OVA epitope limited to infected cells, suggesting that protective CD4 + T cells recognize infected cell debris rather than infected cells themselves. While MCMV-mOVA protected acutely against MuHV-4-mOVA, long-term protection was incomplete, even when OVAspecific CD8 + T cells and B cells were also primed. Thus, even optimized single-target vaccines may poorly reduce long-term c-herpesvirus infections. OVA expression by MCMV and MuHV-4 in vivoMCMV-OVA and MCMV-mOVA were attenuated for replication in vivo, after either intranasal (i.n.; Figure 2a) or intraperitoneal (i.p.; Figure 2b) inoculation, as described for similar IE2 disruptions. 29 The attenuation was less marked after i.p. infection, so we used this for immunization. MCMV-mOVA induced readily detectable OVA-specific IgG 2a -although little IgG 1 (Figure 2c). MCMV-OVA also induced OVA-specific antibody, but 333 J Yunis et al.CD4 + T cell vaccination SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article.

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Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

Cited by 5 publications

References 41 publications

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

The Chemokine Receptor CXCR3 Promotes CD8+ T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection

Membrane association of a model CD4⁺ T‐cell vaccine antigen confers enhanced yet incomplete protection against murid herpesvirus‐4 infection

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Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

Cited by 5 publications

References 41 publications

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

The Chemokine Receptor CXCR3 Promotes CD8+ T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection

Membrane association of a model CD4+ T‐cell vaccine antigen confers enhanced yet incomplete protection against murid herpesvirus‐4 infection

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Membrane association of a model CD4⁺ T‐cell vaccine antigen confers enhanced yet incomplete protection against murid herpesvirus‐4 infection