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: To further investigate the functionality of these delayed antibody responses, we assessed whether these responses could expand after a boosting immunization. C57BL/6 mice were immunized i.m. with 1010 vp of Ad26-SIV Env and depleted of CD4+ T cells on day −1 or left untreated as a control (Fig. 3A). Four months after the primary immunization, mice were boosted i.m. with 1010 vp of Ad5-SIV Env (Fig. 3A). One month after the boosting immunization, the anti-CD4 antibody-treated and untreated mice had equivalent median SIV Env-specific endpoint titers (Fig. 3B), which reflected equivalent mean fold expansions of 54-fold and 43-fold, respectively (P = 0.8) (Fig. 3C). As a final measure of functional capacity, we assessed the ability of these delayed antibodies to neutralize an SIV Env-expressing pseudovirus. No SIV-specific neutralizing antibodies in anti-CD4-treated mice were detected at 1 month postimmunization (Fig. 3D), which is consistent with the lack of Env-specific binding antibodies at this time point (Fig. 1B). However, by 4 months postimmunization, anti-CD4-treated mice had median neutralizing antibody titers that were not significantly different from those in undepleted vaccinated mice (P = 0.9) (Fig. 3D). In both groups, neutralizing antibody titers increased following the boosting immunization, and again, no differences between the two groups were observed (Fig. 3D). Collectively, these data demonstrate that the delayed antibody responses that developed following depletion of CD4+ T cells at the time of primary Ad vector immunization have no detectable defects in boosting capacity, the ability to acquire functional neutralization capacity, isotype proportions, or antigen-binding avidity.
Affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.