Shortened intervals during Heterologous boosting preserve memory CD8 t cell function but compromise longevity

Emily A. Thompson, Lalit K. Beura, Christine E. Nelson, Kristin G. Anderson, Vaiva Vezys

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Developing vaccine strategies to generate high numbers of Ag-specific CD8 T cells may be necessary for protection against recalcitrant pathogens. 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. Shortboosted 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, shortboosted Ag-specific CD8 T cells continue to contract gradually over time, which correlates to metabolic differences between shortand 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.

Original languageEnglish (US)
Pages (from-to)3054-3063
Number of pages10
JournalJournal of Immunology
Issue number7
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant DP2OD006473 (to V.V.) and National Institutes of Health Immunology Grant T32AI007313 (to E.A.T. and C.E.N.). We thank Dr. David Masopust for discussion and critical reading of the manuscript and Dr. Kathryn Fraser and Eric Hanse for discussion of metabolic assays.

Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.


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