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Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.

Combadiere B, Boissonnas A, Carcelain G, Lefranc E, Samri A, Bricaire F, Debre P, Autran B - J. Exp. Med. (2004)

Bottom Line: Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all.The number of recalls did not affect the persistence of residual effector-memory T cells.Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Paris, France.

ABSTRACT
Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-gamma-producing effector-memory and proliferative memory T cells were compared in 79 vaccinees 13-25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-gamma-producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector-memory T cells. Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.

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Lack of influence of vaccinia recalls and time since last immunization on the long-term persistence of IFN-γ–producing effector–memory T cells. Distribution of vaccinia-specific responses in 44 vaccinated individuals with a known vaccination history, according to the number of recalls they received up to 13 yr ago for both ELISpot (a) and proliferation (b) assays and according to time since last immunization for ELISpot (c) and proliferation (d) assays. The same three groups described in Fig. 3 were distinguished according to time since priming: 10–25, 25–45, and >45 yr. For all graphs, statistical analysis was performed as in Fig. 5.
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fig6: Lack of influence of vaccinia recalls and time since last immunization on the long-term persistence of IFN-γ–producing effector–memory T cells. Distribution of vaccinia-specific responses in 44 vaccinated individuals with a known vaccination history, according to the number of recalls they received up to 13 yr ago for both ELISpot (a) and proliferation (b) assays and according to time since last immunization for ELISpot (c) and proliferation (d) assays. The same three groups described in Fig. 3 were distinguished according to time since priming: 10–25, 25–45, and >45 yr. For all graphs, statistical analysis was performed as in Fig. 5.

Mentions: It is a tenet of vaccinology that booster inoculations help to maintain high levels of long-term effector–memory immune responses. Smallpox vaccination schedules typically imposed vaccinia priming at 1 yr and recall injections at 11 and 21 yr (16, 18). Detailed information about prior vaccination was available for only 44 of the 79 vaccinees. Thus, we classified them according to the number of vaccinations they received: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. All had their first vaccination at the age of 1 yr. We found that the number of immunizations did not affect either the rapid effector–memory response (Fig. 6 a) or the vaccinia-specific memory T cell proliferation (Fig. 6 b).


Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.

Combadiere B, Boissonnas A, Carcelain G, Lefranc E, Samri A, Bricaire F, Debre P, Autran B - J. Exp. Med. (2004)

Lack of influence of vaccinia recalls and time since last immunization on the long-term persistence of IFN-γ–producing effector–memory T cells. Distribution of vaccinia-specific responses in 44 vaccinated individuals with a known vaccination history, according to the number of recalls they received up to 13 yr ago for both ELISpot (a) and proliferation (b) assays and according to time since last immunization for ELISpot (c) and proliferation (d) assays. The same three groups described in Fig. 3 were distinguished according to time since priming: 10–25, 25–45, and >45 yr. For all graphs, statistical analysis was performed as in Fig. 5.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211784&req=5

fig6: Lack of influence of vaccinia recalls and time since last immunization on the long-term persistence of IFN-γ–producing effector–memory T cells. Distribution of vaccinia-specific responses in 44 vaccinated individuals with a known vaccination history, according to the number of recalls they received up to 13 yr ago for both ELISpot (a) and proliferation (b) assays and according to time since last immunization for ELISpot (c) and proliferation (d) assays. The same three groups described in Fig. 3 were distinguished according to time since priming: 10–25, 25–45, and >45 yr. For all graphs, statistical analysis was performed as in Fig. 5.
Mentions: It is a tenet of vaccinology that booster inoculations help to maintain high levels of long-term effector–memory immune responses. Smallpox vaccination schedules typically imposed vaccinia priming at 1 yr and recall injections at 11 and 21 yr (16, 18). Detailed information about prior vaccination was available for only 44 of the 79 vaccinees. Thus, we classified them according to the number of vaccinations they received: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. All had their first vaccination at the age of 1 yr. We found that the number of immunizations did not affect either the rapid effector–memory response (Fig. 6 a) or the vaccinia-specific memory T cell proliferation (Fig. 6 b).

Bottom Line: Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all.The number of recalls did not affect the persistence of residual effector-memory T cells.Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Paris, France.

ABSTRACT
Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-gamma-producing effector-memory and proliferative memory T cells were compared in 79 vaccinees 13-25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-gamma-producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector-memory T cells. Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.

Show MeSH
Related in: MedlinePlus