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

被引:52
作者
Devito, C
Zuber, B
Schröder, U
Benthin, R
Okuda, K
Broliden, K
Wahren, B
Hinkula, J
机构
[1] Karolinska Inst, Dept Virol, Ctr Microbiol & Tumor Biol, Solna, Sweden
[2] Eurocine, Stockholm, Sweden
[3] Yokohama City Univ, Sch Med, Dept Bacteriol, Yokohama, Kanagawa 232, Japan
[4] Huddinge Univ Hosp, Div Clin Virol, S-14186 Huddinge, Sweden
关键词
D O I
10.4049/jimmunol.173.11.7078
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:7078 / 7089
页数:12
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