Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity
Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity
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DOI：
10.4049/jimmunol.173.11.7078
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Hinkula, J
中科院分区：
文献类型：
--
作者：
Devito, C;Zuber, B;Hinkula, J
将鼻内DNA疫苗初免接着gp 41肽加强免疫与gp 41肽和对照免疫进行比较。免疫后检测血清中HIV-1特异性IgG和伊加以及粪便、阴道和肺分泌物中的伊加。通过检测免疫小鼠脾脏和局部淋巴结中HIV-1 gp 41和CCR 5特异性抗体和分泌IgG/IgA的B淋巴细胞的存在，研究了加强免疫后长达12个月的长期体液免疫。除了全身免疫应答外，还获得了肠、阴道和肺中的长期IgA特异性应答。仅用gp 41肽和L3佐剂免疫的小鼠产生了长期的gp 41特异性血清IgG全身性应答，尽管时间较短（1-9个月），以及长期的粘膜gp 41特异性伊加免疫。诱导HIV-1中和血清抗体，其在加强免疫后12个月仍存在。HIV-1 SF 2中和粪便和肺伊加仅在DNA致敏小鼠组中可检测到。鼻内DNA初免，然后是一种肽/L3佐剂加强免疫，但不是肽初免，然后是DNA加强免疫，能够诱导B细胞记忆和HIV-1中和抗体，持续小鼠寿命的至少一半。
An intranasal DNA, vaccine prime followed by a gp41 peptide booster immunization was compared with gp41 peptide and control immunizations. Serum HIV-1-specific IgG and IgA as well as IgA in feces and vaginal and lung secretions were detected after immunizations. Long-term humoral immunity was studied for up to 12 mo after the booster immunization by testing the presence of HIV-1 gp41- and CCR5-specific Abs and IgG/IgA-secreting B lymphocytes in spleen and regional lymph nodes in immunized mice. A long-term IgA-specific response in the intestines, vagina, and lungs was obtained in addition to a systemic immune response. Mice immunized only with gp41 peptides and L3 adjuvant developed a long-term gp41-specific serum IgG response systemically, although over a shorter period (1-9 mo), and long-term mucosal gp41-specific IgA immunity. HIV-1-neutralizing serum Abs were induced that were still present 12 mo after booster immunization. HIV-1 SF2-neutralizing fecal and lung IgA was detectable only in the DNA-primed mouse groups. Intranasal DNA prime followed by one peptide/L3 adjuvant booster immunization, but not a peptide prime followed by a DNA booster, was able to induce B cell memory and HIV-1-neutralizing Abs for at least half of a mouse's life span.