Flt3 ligand enhances the immunogenicity of a gag-based HIV-1 vaccine

Vladimir M Pisarev , Prahlad Parajuli , R.Lee Mosley , Jennifer Sublet , Linda Kelsey , Prem S Sarin , Daniel H Zimmerman , M.Douglas Winship , James E Talmadge
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引用次数: 23

Abstract

Liposomes and Flt3 ligand (Flt3L), a ligand for the fms-like tyrosine kinase receptor Flt3/ FLK2, can augment the immune response to an HIV peptide vaccine. The HGP-30 peptide used in these studies is a synthetic peptide that corresponds to a highly conserved region of HIV-1 p17 gag (amino acids 86–115). Mice were immunized with HGP-30 or HGP-30 conjugated to keyhole limpet hemocyanin (KLH) and delayed-type hypersensitivity (DTH) responses, antibody (IgG) amount and antigen-specific proliferative responses by spleen cells were used to monitor the immune response. Daily injections of Flt3L prior to HGP-30 administration enhanced significantly an antigen-specific lymphocyte proliferation response when compared with Flt3L, HGP-30 alone or HGP-30 containing liposomes. Intravenous administration of HGP-30 was superior to intramuscular (i.m.) immunization for the induction of DTH responses. The HGP-30/KLH containing liposomes enhanced both DTH and antibody responses, while liposomes containing HGP-30 peptide elicited only T cell responses. In these studies, either Flt3L or liposomes increased DTH responses compared with the i.m. injection of the HGP-30 vaccine alone.

Flt3配体增强了基于gag的HIV-1疫苗的免疫原性
脂质体和Flt3配体(Flt3L),一种fms样酪氨酸激酶受体Flt3/ FLK2的配体,可以增强对HIV肽疫苗的免疫应答。这些研究中使用的HGP-30肽是一种合成肽,与HIV-1 p17 gag的高度保守区域(氨基酸86-115)相对应。用HGP-30或HGP-30偶联锁眼帽蓝蛋白(KLH)免疫小鼠,观察延迟型超敏反应(DTH)、抗体(IgG)量和脾细胞抗原特异性增殖反应。与单用Flt3L、HGP-30或含脂质体的HGP-30相比,在给药前每日注射Flt3L可显著增强抗原特异性淋巴细胞增殖反应。静脉注射HGP-30在诱导DTH反应方面优于肌肉注射(i.m)免疫。含有HGP-30/KLH的脂质体增强了DTH和抗体反应,而含有HGP-30肽的脂质体仅引起T细胞反应。在这些研究中,与单独注射HGP-30疫苗相比,Flt3L或脂质体都增加了DTH反应。
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