Abstract
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear. Here, we show, using a cellular vaccine carrying foreign protein antigen plus iNKT cell glycolipid antigen, designated as artificial adjuvant vector cells (aAVCs), that mature XCR1− DCs in situ elicit not only ordinal antigen-specific CD4+T cells, but also CD4+ Tfh and germinal center, resulted in inducing long-term antibody production. As a mechanism for leading the long-term antibody production by aAVC, memory CD4+ Tfh cells but not iNKTfh cells played an important role in a Bcl6 dependent manner. To develop it for influenza infection, we established influenza hemagglutinin-carrying aAVC (aAVC-HA) and found that all the mice vaccinated with aAVC-HA were protected from life-threatening influenza infection. Thus, the in vivo DC targeting therapy by aAVC would be useful for protection against viral infection.
Highlights
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear
We previously demonstrated the efficacy of a cellular vaccine comprised of OVA mRNA-transfected CD1d-allogeneic cells loaded with α-GalCer, which we termed OVA-expressing artificial adjuvant vector cells[8]
We previously reported that antigen-specific CD8+ cytotoxic lymphocytes (CTL) were generated after administration of adjuvant vector cells (aAVCs)-OVA though cross-presentation by CD8a+ CD11c+ DCs in situ[9]
Summary
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear. We show, using a cellular vaccine carrying foreign protein antigen plus iNKT cell glycolipid antigen, designated as artificial adjuvant vector cells (aAVCs), that mature XCR1− DCs in situ elicit ordinal antigen-specific CD4+ T cells, and CD4+ Tfh and germinal center, resulted in inducing long-term antibody production. As a mechanism for leading the long-term antibody production by aAVC, memory CD4+ Tfh cells but not iNKTfh cells played an important role in a Bcl[6] dependent manner To develop it for influenza infection, we established influenza hemagglutinin-carrying aAVC (aAVC-HA) and found that all the mice vaccinated with aAVC-HA were protected from life-threatening influenza infection. The development of new vaccine adjuvants has been intensively explored to enhance the efficacy of weak antigens and broaden the immune response profile, leading to generation of high titer anti-viral antibodies. We investigated the involvement of Bcl-6 in Tfh or iNKTfh cells that would provide help for B cells and assessed whether an aAVC vaccine could protect from influenza virus infection
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