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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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Vaccinia-specific effector–memory response vanishes 45 yr after priming. (a and b) Distribution of vaccinia-specific responses in vaccinated individuals according to time since priming for ELISpot assay (a) and proliferation assay (b). Three groups were distinguished according to time since priming, 25–35, 36–45, and >45 yr, and were compared with unvaccinated unexposed donors. A precise, documented vaccination history was available for only 44 individuals as follows: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. For all graphs, statistical analysis used the χ2 test. Statistical significance was set at P < 0.05 (**). ns, not significant.
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fig5: Vaccinia-specific effector–memory response vanishes 45 yr after priming. (a and b) Distribution of vaccinia-specific responses in vaccinated individuals according to time since priming for ELISpot assay (a) and proliferation assay (b). Three groups were distinguished according to time since priming, 25–35, 36–45, and >45 yr, and were compared with unvaccinated unexposed donors. A precise, documented vaccination history was available for only 44 individuals as follows: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. For all graphs, statistical analysis used the χ2 test. Statistical significance was set at P < 0.05 (**). ns, not significant.

Mentions: Because murine models of lymphocytic choriomeningitis virus infection indicate that the quality and quantity of T cell priming during the first encounter with antigen might determine the size of the memory T cell pool (3), we investigated whether a higher frequency of memory responses in vaccinees was associated with a shorter delay from priming. We distinguished three groups according to time since priming: 25–35, 36–45, and >45 yr, with 20, 32, and 27 vaccinees per group, respectively (Fig. 5, a and b). The proportion of IFN-γ–producing effector–memory T cells was highest in the 36–45 yr group (12 out of 32 or 37.5%), and lower (5 out of 21 or 24%), but not significantly so, among the group with the least time since priming (25–35 yr) (Fig. 5 a). Vaccinia-specific effector–memory responses tended to vanish in the group primed more than 45 yr earlier (2 out of 27 or 7.5%): they did not differ from the frequencies observed in the unvaccinated group and were significantly lower than in the 25–35 and 36–45 yr groups (P = 0.0068 and 0.019, respectively) (Fig. 5 a). In contrast, the proliferative vaccinia-specific memory T cells remained stable whatever the time since priming with 73, 73, and 70% of responders in each group (Fig. 5 b). Thus, more than 45 yr after priming the intensity of IFN-γ–producing effector–memory response tended to revert to that observed in unvaccinated individuals.


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)

Vaccinia-specific effector–memory response vanishes 45 yr after priming. (a and b) Distribution of vaccinia-specific responses in vaccinated individuals according to time since priming for ELISpot assay (a) and proliferation assay (b). Three groups were distinguished according to time since priming, 25–35, 36–45, and >45 yr, and were compared with unvaccinated unexposed donors. A precise, documented vaccination history was available for only 44 individuals as follows: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. For all graphs, statistical analysis used the χ2 test. Statistical significance was set at P < 0.05 (**). ns, not significant.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Vaccinia-specific effector–memory response vanishes 45 yr after priming. (a and b) Distribution of vaccinia-specific responses in vaccinated individuals according to time since priming for ELISpot assay (a) and proliferation assay (b). Three groups were distinguished according to time since priming, 25–35, 36–45, and >45 yr, and were compared with unvaccinated unexposed donors. A precise, documented vaccination history was available for only 44 individuals as follows: one (n = 12), two (n = 23), three (n = 4), four (n = 4), or five (n = 1) immunizations. For all graphs, statistical analysis used the χ2 test. Statistical significance was set at P < 0.05 (**). ns, not significant.
Mentions: Because murine models of lymphocytic choriomeningitis virus infection indicate that the quality and quantity of T cell priming during the first encounter with antigen might determine the size of the memory T cell pool (3), we investigated whether a higher frequency of memory responses in vaccinees was associated with a shorter delay from priming. We distinguished three groups according to time since priming: 25–35, 36–45, and >45 yr, with 20, 32, and 27 vaccinees per group, respectively (Fig. 5, a and b). The proportion of IFN-γ–producing effector–memory T cells was highest in the 36–45 yr group (12 out of 32 or 37.5%), and lower (5 out of 21 or 24%), but not significantly so, among the group with the least time since priming (25–35 yr) (Fig. 5 a). Vaccinia-specific effector–memory responses tended to vanish in the group primed more than 45 yr earlier (2 out of 27 or 7.5%): they did not differ from the frequencies observed in the unvaccinated group and were significantly lower than in the 25–35 and 36–45 yr groups (P = 0.0068 and 0.019, respectively) (Fig. 5 a). In contrast, the proliferative vaccinia-specific memory T cells remained stable whatever the time since priming with 73, 73, and 70% of responders in each group (Fig. 5 b). Thus, more than 45 yr after priming the intensity of IFN-γ–producing effector–memory response tended to revert to that observed in unvaccinated individuals.

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