TY - JOUR
T1 - Shortened intervals during Heterologous boosting preserve memory CD8 t cell function but compromise longevity
AU - Thompson, Emily A.
AU - Beura, Lalit K.
AU - Nelson, Christine E.
AU - Anderson, Kristin G.
AU - Vezys, Vaiva
N1 - Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1501797
DO - 10.4049/jimmunol.1501797
M3 - Article
C2 - 26903479
AN - SCOPUS:84962585729
SN - 0022-1767
VL - 196
SP - 3054
EP - 3063
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -