{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:06:58Z","timestamp":1767650818088,"version":"3.38.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Experimental CMV-based vaccine vectors expressing a single MHC class I\u2013restricted high-avidity epitope provided strong, T cell\u2013dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2. The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context. Immune protection was matched by Ag-induced, long-term expansion of effector memory CD8 T cells, regardless of epitope avidity. We explained this pattern by observing regularities in Ag competition, where responses to high-avidity epitopes outcompeted weaker ones expressed later in the replicative cycle of the virus. Conversely, robust and early expression of a low-avidity epitope compensated its weak intrinsic antigenicity, resulting in strong and sustained immunity and immune protection.<\/jats:p>","DOI":"10.4049\/jimmunol.1602115","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:30:33Z","timestamp":1501720233000},"page":"1737-1747","source":"Crossref","is-referenced-by-count":23,"title":["Immune Protection by a Cytomegalovirus Vaccine Vector Expressing a Single Low-Avidity Epitope"],"prefix":"10.1093","volume":"199","author":[{"given":"Lisa","family":"Borkner","sequence":"first","affiliation":[{"name":"Research Group Immune Aging and Chronic Infections, Department of Vaccinology, Helmholtz Centre for Infection Research , 38124 Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-0322","authenticated-orcid":false,"given":"Katarzyna M","family":"Sitnik","sequence":"additional","affiliation":[{"name":"Research Group Immune Aging and Chronic Infections, Department of Vaccinology, Helmholtz Centre for Infection Research , 38124 Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iryna","family":"Dekhtiarenko","sequence":"additional","affiliation":[{"name":"Research Group Immune Aging and Chronic Infections, Department of Vaccinology, Helmholtz Centre for Infection Research , 38124 Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Kathrin","family":"Pulm","sequence":"additional","affiliation":[{"name":"Research Group Immune Aging and Chronic Infections, Department of Vaccinology, Helmholtz Centre for Infection Research , 38124 Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronny","family":"Tao","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital D\u00fcsseldorf, Heinrich Heine University , 40225 D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-9144","authenticated-orcid":false,"given":"Ingo","family":"Drexler","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital D\u00fcsseldorf, Heinrich Heine University , 40225 D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-778X","authenticated-orcid":false,"given":"Luka","family":"Cicin-Sain","sequence":"additional","affiliation":[{"name":"Research Group Immune Aging and Chronic Infections, Department of Vaccinology, Helmholtz Centre for Infection Research , 38124 Braunschweig,","place":["Germany"]},{"name":"Institute for Virology, Medical School Hannover , 30625 Hannover,","place":["Germany"]},{"name":"German Center for Infection Research, Hannover-Braunschweig Site , 38124 Braunschweig,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2025030614270999800_r1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.semcancer.2007.06.006","article-title":"Mobilizing the low-avidity T cell repertoire to kill tumors","volume":"17","author":"McMahan","year":"2007","journal-title":"Semin. Cancer Biol."},{"key":"2025030614270999800_r2","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1002\/eji.201242606","article-title":"Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies","volume":"42","author":"Aleksic","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"2025030614270999800_r3","doi-asserted-by":"crossref","first-page":"21674","DOI":"10.1038\/srep21674","article-title":"Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection","volume":"6","author":"Marzi","year":"2016","journal-title":"Sci. Rep."},{"key":"2025030614270999800_r4","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature10003","article-title":"Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine","volume":"473","author":"Hansen","year":"2011","journal-title":"Nature"},{"key":"2025030614270999800_r5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nm.1935","article-title":"Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge","volume":"15","author":"Hansen","year":"2009","journal-title":"Nat. Med."},{"key":"2025030614270999800_r6","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1128\/JVI.78.5.2255-2264.2004","article-title":"Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses","volume":"78","author":"Karrer","year":"2004","journal-title":"J. Virol."},{"key":"2025030614270999800_r7","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.4049\/jimmunol.1203173","article-title":"The context of gene expression defines the immunodominance hierarchy of cytomegalovirus antigens","volume":"190","author":"Dekhtiarenko","year":"2013","journal-title":"J. Immunol."},{"key":"2025030614270999800_r8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/mi.2016.48","article-title":"Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung","volume":"10","author":"Morabito","year":"2017","journal-title":"Mucosal Immunol."},{"key":"2025030614270999800_r9","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.4049\/jimmunol.1302523","article-title":"A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis","volume":"193","author":"Beverley","year":"2014","journal-title":"J. Immunol."},{"key":"2025030614270999800_r10","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1158\/2326-6066.CIR-14-0044","article-title":"Cytomegalovirus-based vaccine expressing a modified tumor antigen induces potent tumor-specific CD8(+) T-cell response and protects mice from melanoma","volume":"3","author":"Qiu","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"2025030614270999800_r11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/CJI.0b013e3182585d50","article-title":"A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer","volume":"35","author":"Klyushnenkova","year":"2012","journal-title":"J. Immunother."},{"key":"2025030614270999800_r12","first-page":"2675","volume-title":"Fields Virology.","author":"Pass","year":"2001"},{"key":"2025030614270999800_r13","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1084\/jem.20050882","article-title":"Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects","volume":"202","author":"Sylwester","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025030614270999800_r14","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.4049\/jimmunol.170.4.2022","article-title":"Memory inflation: continuous accumulation of antiviral CD8+ T cells over time","volume":"170","author":"Karrer","year":"2003","journal-title":"J. Immunol."},{"key":"2025030614270999800_r15","doi-asserted-by":"crossref","first-page":"11495","DOI":"10.1128\/JVI.74.24.11495-11503.2000","article-title":"Enrichment of immediate-early 1 (m123\/pp89) peptide-specific CD8 T cells in a pulmonary CD62L(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs","volume":"74","author":"Holtappels","year":"2000","journal-title":"J. Virol."},{"key":"2025030614270999800_r16","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1002\/eji.200425534","article-title":"Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection","volume":"35","author":"Sierro","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"2025030614270999800_r17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4049\/jimmunol.169.1.359","article-title":"The murine cytomegalovirus immunomodulatory gene m152 prevents recognition of infected cells by M45-specific CTL but does not alter the immunodominance of the M45-specific CD8 T cell response in vivo","volume":"169","author":"Gold","year":"2002","journal-title":"J. Immunol."},{"key":"2025030614270999800_r18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.4049\/jimmunol.177.1.450","article-title":"Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection","volume":"177","author":"Munks","year":"2006","journal-title":"J. Immunol."},{"key":"2025030614270999800_r19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-med-042010-085643","article-title":"New paradigms for HIV\/AIDS vaccine development","volume":"63","author":"Picker","year":"2012","journal-title":"Annu. Rev. Med."},{"key":"2025030614270999800_r20","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.4049\/jimmunol.160.11.5410","article-title":"T cells expressing receptors of different affinity for antigen ligands reveal a unique role for p59fyn in T cell development and optimal stimulation of T cells by antigen","volume":"160","author":"Utting","year":"1998","journal-title":"J. Immunol."},{"key":"2025030614270999800_r21","first-page":"493","volume-title":"Methods in Microbiology","author":"Podlech","year":"2002"},{"key":"2025030614270999800_r22","doi-asserted-by":"crossref","first-page":"10346","DOI":"10.1128\/JVI.00545-11","article-title":"Virus progeny of murine cytomegalovirus bacterial artificial chromosome pSM3fr show reduced growth in salivary glands due to a fixed mutation of MCK-2","volume":"85","author":"Jordan","year":"2011","journal-title":"J. Virol."},{"key":"2025030614270999800_r23","doi-asserted-by":"crossref","first-page":"9567","DOI":"10.1128\/JVI.72.12.9567-9574.1998","article-title":"Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity","volume":"72","author":"Blaney","year":"1998","journal-title":"J. Virol."},{"key":"2025030614270999800_r24","first-page":"16.16.11","volume-title":"Current Protocols in Molecular Biology.","author":"Moss","year":"1991"},{"key":"2025030614270999800_r25","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.1128\/JVI.73.9.7619-7626.1999","article-title":"The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL\/6 mice is almost entirely directed against a single immunodominant determinant","volume":"73","author":"Wallace","year":"1999","journal-title":"J. Virol."},{"key":"2025030614270999800_r26","doi-asserted-by":"crossref","first-page":"7056","DOI":"10.1128\/JVI.73.8.7056-7060.1999","article-title":"Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution","volume":"73","author":"Wagner","year":"1999","journal-title":"J. Virol."},{"key":"2025030614270999800_r27","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.1128\/JVI.77.10.5557-5570.2003","article-title":"Role of murine cytomegalovirus US22 gene family members in replication in macrophages","volume":"77","author":"M\u00e9nard","year":"2003","journal-title":"J. Virol."},{"key":"2025030614270999800_r28","first-page":"51","article-title":"Live viral vectors: vaccinia virus","volume":"87","author":"Staib","year":"2003","journal-title":"Methods Mol. Med."},{"key":"2025030614270999800_r29","doi-asserted-by":"crossref","first-page":"9492","DOI":"10.1128\/JVI.79.15.9492-9502.2005","article-title":"Frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host","volume":"79","author":"Cicin-Sain","year":"2005","journal-title":"J. Virol."},{"key":"2025030614270999800_r30","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/0092-8674(91)90037-Y","article-title":"Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein","volume":"66","author":"Del Val","year":"1991","journal-title":"Cell"},{"key":"2025030614270999800_r31","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1006\/geno.1995.1074","article-title":"Genetic mapping of Cmv1 in the region of mouse chromosome 6 encoding the NK gene complex-associated loci Ly49 and musNKR-P1","volume":"27","author":"Scalzo","year":"1995","journal-title":"Genomics"},{"key":"2025030614270999800_r32","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1070884","article-title":"Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors","volume":"296","author":"Arase","year":"2002","journal-title":"Science"},{"key":"2025030614270999800_r33","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1128\/JVI.06042-11","article-title":"The NK cell response to mouse cytomegalovirus infection affects the level and kinetics of the early CD8(+) T-cell response","volume":"86","author":"Mitrovi\u0107","year":"2012","journal-title":"J. Virol."},{"key":"2025030614270999800_r34","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.4049\/jimmunol.1203151","article-title":"Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection","volume":"190","author":"Farrington","year":"2013","journal-title":"J. Immunol."},{"key":"2025030614270999800_r35","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00430-015-0404-3","article-title":"Identification of an atypical CD8 T cell epitope encoded by murine cytomegalovirus ORF-M54 gaining dominance after deletion of the immunodominant antiviral CD8 T cell specificities","volume":"204","author":"Holtappels","year":"2015","journal-title":"Med. Microbiol. Immunol. (Berl.)"},{"key":"2025030614270999800_r36","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.4049\/jimmunol.1200966","article-title":"Priming of CD8+ T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation","volume":"190","author":"Busche","year":"2013","journal-title":"J. Immunol."},{"key":"2025030614270999800_r37","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1002\/eji.201041075","article-title":"Batf3 transcription factor-dependent DC subsets in murine CMV infection: differential impact on T-cell priming and memory inflation","volume":"41","author":"Torti","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"2025030614270999800_r38","doi-asserted-by":"crossref","first-page":"e1002313","DOI":"10.1371\/journal.ppat.1002313","article-title":"Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection","volume":"7","author":"Torti","year":"2011","journal-title":"PLoS Pathog."},{"key":"2025030614270999800_r39","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1099\/vir.0.031815-0","article-title":"Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency","volume":"92","author":"Seckert","year":"2011","journal-title":"J. Gen. Virol."},{"key":"2025030614270999800_r40","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature12519","article-title":"Immune clearance of highly pathogenic SIV infection","volume":"502","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"2025030614270999800_r41","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00430-012-0273-y","article-title":"Viral latency drives \u2018memory inflation\u2019: a unifying hypothesis linking two hallmarks of cytomegalovirus infection","volume":"201","author":"Seckert","year":"2012","journal-title":"Med. Microbiol. Immunol. (Berl.)"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/5\/1737\/61582216\/ji1602115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/5\/1737\/61582216\/ji1602115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T16:22:09Z","timestamp":1741278129000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/199\/5\/1737\/7974765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,1]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1602115","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"type":"print","value":"0022-1767"},{"type":"electronic","value":"1550-6606"}],"subject":[],"published-other":{"date-parts":[[2017,9]]},"published":{"date-parts":[[2017,9,1]]}}}