J Virol. 2016 May; 90(9):4278-4288.

PubMed ID: 26865713

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

We have recently demonstrated that CD4(+)T cell help is required at the time of adenovirus (Ad) vector immunization for the development of functional CD8(+)T cell responses, but the temporal requirement for CD4(+)T cell help for the induction of antibody responses remains unclear. Here we demonstrate that induction of antibody responses in C57BL/6 mice can occur at a time displaced from the time of Ad vector immunization by depletion of CD4(+)T cells. Transient depletion of CD4(+)T cells at the time of immunization delays the development of antigen-specific antibody responses but does not permanently impair their development or induce tolerance against the transgene. Upon CD4(+)T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals. These delayed antibody responses exhibit no functional defects with regard to isotype, functional avidity, expansion after boosting immunization, or the capacity to neutralize a simian immunodeficiency virus (SIV) Env-expressing pseudovirus. The development of this delayed transgene-specific antibody response is temporally linked to the expansion of de novo antigen-specific CD4(+)T cell responses, which develop after transient depletion of CD4(+)T cells. These data demonstrate that functional vaccine-elicited antibody responses can be induced even if CD4(+)T cell help is provided at a time markedly separated from the time of vaccination.