Table 1 Experimental strategies to... | American Society of Hematology

Table 1

Experimental strategies to optimize vaccine T-cell memory

Approach	CD8 T-cell memory		References
Approach	Tem	Tcm	References
Heterologous prime boost*			58
DNA prime viral vector boost†	++	++	61, 101,–103
Multiple heterologous recombinant viral vector	+++	++	104,,–107
Mucosal heterologous prime boost	+++	++	61, 108
Persistent replicating vectors	+++	+	9, 109
Concurrent heterologous vaccination	++	++
Maximize CD4⁺-proficient help
Epitope enhancement, CD40L, agonist CD27 Ab	++	+++	97, 98, 100, 110
Cytokines and immunomodulatory molecules
IL-12	+++	+	111
IL-7	++	+++	89, 90
IL-15	++	++	112,–114
IL-7 or IL-15 plus IL-21	+	++	94, 95
α-galactosylceramide (αGalCer) activation of NKT cell type I	+++	++	115
Synergistic TLR combinations in prime boost	+++	+	116, 117
Dendritic cell targeting combined with synergistic TLR ligands	+++	++
Wnt 3a or GSK3β inhibitors		Tscm	54
Provide effective costimulation
TNFSF: 41BBL, OX40L, CD70	++	++	118, 119
Block negative costimulation
Anti–CTLA-4, anti–BTLA-4, anti-PD1	+++	++	120, 121
Push-pull approaches
GM-CSF and CD40L, plus IL-13Rα2–Fc	+++	+++	97
41BBL plus anti–CTLA-4,	+++	+++	119
TLR combinations plus anti–IL-10	+++	+
Dendritic cell immunization (Flt3L in vitro expansion)			34
TLR 3 plus TLR7/8 activation	+++	+	116, 122
Adenovirus transfection	++	++	123
miRNA–SOCS-1 inhibition	+	++
Repeated immunization at short intervals with multiepitope fusion peptides (Bacillus anthracis lethal factor Lfn) plus protective antigen (PA)	++	++	59

Approach	CD8 T-cell memory		References
Approach	Tem	Tcm	References
Heterologous prime boost*			58
DNA prime viral vector boost†	++	++	61, 101,–103
Multiple heterologous recombinant viral vector	+++	++	104,,–107
Mucosal heterologous prime boost	+++	++	61, 108
Persistent replicating vectors	+++	+	9, 109
Concurrent heterologous vaccination	++	++
Maximize CD4⁺-proficient help
Epitope enhancement, CD40L, agonist CD27 Ab	++	+++	97, 98, 100, 110
Cytokines and immunomodulatory molecules
IL-12	+++	+	111
IL-7	++	+++	89, 90
IL-15	++	++	112,–114
IL-7 or IL-15 plus IL-21	+	++	94, 95
α-galactosylceramide (αGalCer) activation of NKT cell type I	+++	++	115
Synergistic TLR combinations in prime boost	+++	+	116, 117
Dendritic cell targeting combined with synergistic TLR ligands	+++	++
Wnt 3a or GSK3β inhibitors		Tscm	54
Provide effective costimulation
TNFSF: 41BBL, OX40L, CD70	++	++	118, 119
Block negative costimulation
Anti–CTLA-4, anti–BTLA-4, anti-PD1	+++	++	120, 121
Push-pull approaches
GM-CSF and CD40L, plus IL-13Rα2–Fc	+++	+++	97
41BBL plus anti–CTLA-4,	+++	+++	119
TLR combinations plus anti–IL-10	+++	+
Dendritic cell immunization (Flt3L in vitro expansion)			34
TLR 3 plus TLR7/8 activation	+++	+	116, 122
Adenovirus transfection	++	++	123
miRNA–SOCS-1 inhibition	+	++
Repeated immunization at short intervals with multiepitope fusion peptides (Bacillus anthracis lethal factor Lfn) plus protective antigen (PA)	++	++	59

Although DNA prime and recombinant viral vector boost regimens induce enhanced cell-mediated and humoral immune responses in preclinical models, the results have not yet translated to clinical use. Ongoing efforts to develop new vaccine delivery platforms including DNA electroporation are moving forward toward clinical trial.¹²⁴

†

The cultured ELISPOT assay provides a more sensitive method to enumerate antigen-specific cells not detected in overnight ex vivo assays. This assay may better reveal long-term CD8⁺ T-cell memory responses achieved by prime boost and highlights differences in measuring human CD4⁺ and CD8⁺ T-cell memory.¹²⁵

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