Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses.
Bottom Line: Upon CD4(+)T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals.The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen.These data demonstrate that the time when CD4(+)T cell help signals must be provided is more dynamic and flexible than previously appreciated.
Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.Show MeSH
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Mentions: We sought to identify other immunization regimens where delayed antibody responses may occur following transient depletion of CD4+ T cells. Therefore, we tested adjuvanted soluble protein immunogens as an alternate vaccine platform. C57BL/6 mice were immunized i.m. with 50 μg of trimeric SIV Env gp140 protein formulated in 100 μg of Adju-Phos adjuvant, and mice were either left untreated, depleted of CD4+ T cells at priming, or repeatedly depleted of CD4+ T cells (Fig. 7). This immunization regimen induced robust Env-specific titers at day 30 postimmunization in untreated control mice (Fig. 7), and titers were maintained to day 60. In mice transiently depleted of CD4+ T cells, no Env-specific antibody responses were detected on day 30 postimmunization, but by day 60 postimmunization, these animals had titers equivalent to those in untreated control animals (Fig. 7). Continuous depletion of CD4+ T cells by repeated administration of anti-CD4 antibody prevented the development of Env-specific antibodies on day 60 (Fig. 7). These data demonstrate that a delayed antibody response can occur in the context of multiple immunization regimens and is not a unique characteristic of immunization with replication-incompetent Ad vectors.
Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.