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Heterologous prime-boost-boost immunization has been shown to result in large quantities of functional memory CD8 T cells with protective capacities and long-term stability. Completing the serial immunization steps for heterologous prime-boost-boost can be lengthy, leaving the host vulnerable for an extensive period of time during the vaccination process. We show in this study that shortening the intervals between boosting events to 2 wk results in high numbers of functional and protective Ag-specific CD8 T cells. This protection is comparable to that achieved with long-term boosting intervals. Short-boosted Ag-specific CD8 T cells display a canonical memory T cell signature associated with long-lived memory and have identical proliferative potential to long-boosted T cells Both populations robustly respond to antigenic re-exposure. Despite this, short-boosted Ag-specific CD8 T cells continue to contract gradually over time, which correlates to metabolic differences between short- and long-boosted CD8 T cells at early memory time points. Our studies indicate that shortening the interval between boosts can yield abundant, functional Ag-specific CD8 T cells that are poised for immediate protection; however, this is at the expense of forming stable long-term memory.<\/jats:p>","DOI":"10.4049\/jimmunol.1501797","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T04:13:29Z","timestamp":1456200809000},"page":"3054-3063","source":"Crossref","is-referenced-by-count":28,"title":["Shortened Intervals during Heterologous Boosting Preserve Memory CD8 T Cell Function but Compromise Longevity"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-5249","authenticated-orcid":false,"given":"Emily A","family":"Thompson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-3949","authenticated-orcid":false,"given":"Lalit K","family":"Beura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-4438","authenticated-orcid":false,"given":"Kristin G","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Division of Oncology, Department of Medicine, University of Washington , Seattle, WA 98109"},{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaiva","family":"Vezys","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Center for Immunology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"2025030702152419600_r1","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1126\/science.1241800","article-title":"Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine","volume":"341","author":"Seder","year":"2013","journal-title":"Science"},{"key":"2025030702152419600_r2","doi-asserted-by":"crossref","first-page":"a007252","DOI":"10.1101\/cshperspect.a007252","article-title":"Vaccine design for CD8 T lymphocyte responses","volume":"1","author":"Koup","year":"2011","journal-title":"Cold Spring Harb. 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