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Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses.

Provine NM, Badamchi-Zadeh A, Bricault CA, Penaloza-MacMaster P, Larocca RA, Borducchi EN, Seaman MS, Barouch DH - J. Virol. (2016)

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.

View Article: PubMed Central - PubMed

Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

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Related in: MedlinePlus

Delayed antibody responses develop following immunization with an adjuvanted soluble protein formulated in Adju-Phos but not following immunization with a replication-incompetent poxvirus vector. SIV Env-specific serum antibody titers in C57BL/6 mice immunized intramuscularly with 50 μg of SIV Env gp140 plus Adju-Phos and depleted of CD4+ T cells at the time of immunization (anti-CD4 at prime) or continuously depleted of CD4+ T cells (anti-CD4 repeated) or mice left untreated were determined. Each dot represents an individual mouse, and the line is the median. The horizontal dotted line denotes the limit of detection for the assay (n = 4 to 5/group from one experiment).
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Figure 7: Delayed antibody responses develop following immunization with an adjuvanted soluble protein formulated in Adju-Phos but not following immunization with a replication-incompetent poxvirus vector. SIV Env-specific serum antibody titers in C57BL/6 mice immunized intramuscularly with 50 μg of SIV Env gp140 plus Adju-Phos and depleted of CD4+ T cells at the time of immunization (anti-CD4 at prime) or continuously depleted of CD4+ T cells (anti-CD4 repeated) or mice left untreated were determined. Each dot represents an individual mouse, and the line is the median. The horizontal dotted line denotes the limit of detection for the assay (n = 4 to 5/group from one experiment).

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.


Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses.

Provine NM, Badamchi-Zadeh A, Bricault CA, Penaloza-MacMaster P, Larocca RA, Borducchi EN, Seaman MS, Barouch DH - J. Virol. (2016)

Delayed antibody responses develop following immunization with an adjuvanted soluble protein formulated in Adju-Phos but not following immunization with a replication-incompetent poxvirus vector. SIV Env-specific serum antibody titers in C57BL/6 mice immunized intramuscularly with 50 μg of SIV Env gp140 plus Adju-Phos and depleted of CD4+ T cells at the time of immunization (anti-CD4 at prime) or continuously depleted of CD4+ T cells (anti-CD4 repeated) or mice left untreated were determined. Each dot represents an individual mouse, and the line is the median. The horizontal dotted line denotes the limit of detection for the assay (n = 4 to 5/group from one experiment).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836333&req=5

Figure 7: Delayed antibody responses develop following immunization with an adjuvanted soluble protein formulated in Adju-Phos but not following immunization with a replication-incompetent poxvirus vector. SIV Env-specific serum antibody titers in C57BL/6 mice immunized intramuscularly with 50 μg of SIV Env gp140 plus Adju-Phos and depleted of CD4+ T cells at the time of immunization (anti-CD4 at prime) or continuously depleted of CD4+ T cells (anti-CD4 repeated) or mice left untreated were determined. Each dot represents an individual mouse, and the line is the median. The horizontal dotted line denotes the limit of detection for the assay (n = 4 to 5/group from one experiment).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Show MeSH
Related in: MedlinePlus