Sulczewski Fernando Bandeira, Martino Larissa Alves, Almeida Bianca da Silva, Zaneti Arthur Baruel, Ferreira Natália Soares, Amorim Kelly Nazaré da Silva, Yamamoto Márcio Massao, Apostolico Juliana de Souza, Rosa Daniela Santoro, Boscardin Silvia Beatriz
Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil.
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
Eur J Immunol. 2020 Dec;50(12):1895-1911. doi: 10.1002/eji.202048694. Epub 2020 Jul 26.
Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) αDEC205 (αDEC) and αDCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with αDEC and αDCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro-inflammatory T 1 cell response. Antigen targeting to cDC2s induced T cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the T 1 cell response and induced T 1-like T cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with αDEC and αDCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.
传统树突状细胞(cDCs)专门负责抗原呈递。在小鼠脾脏中,cDCs可分为cDC1s和cDC2s,分别表达内吞受体DEC205和DCIR2。单克隆抗体(mAbs)αDEC205(αDEC)和αDCIR2已与不同抗原融合,以便将抗原递送至cDC1s或cDC2s。我们使用聚肌胞苷酸(Poly(I:C))作为佐剂,用与抗原融合的αDEC和αDCIR2免疫小鼠。在免疫后第3天至第6天分析初始免疫反应。我们还研究了加强剂量的影响。我们的结果表明,靶向cDC1s的抗原促进了促炎性T1细胞反应。靶向cDC2s的抗原诱导了T细胞、生发中心(GCs)和浆细胞分化。加强免疫后,靶向cDC1s的抗原改善了T1细胞反应,并诱导了类似T1的T细胞,导致特异性抗体滴度增加和IgG类别转换。此外,还观察到一群调节性T细胞。加强免疫后,靶向cDC2s的抗原并未改善特异性抗体反应。我们的结果为使用αDEC和αDCIR2融合单克隆抗体给予加强剂量后诱导的免疫反应增添了新信息。这些结果可能对使用重组单克隆抗体的疫苗设计有用。