Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization

Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization
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DOI:
10.1016/s0022-1759(98)00145-8
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发表时间:
1998-11-01
影响因子:
2.2
通讯作者:
Dimmock, NJ
Dimmock, NJ
中科院分区:
医学4区
文献类型:
--
作者:
Durrani, Z;McInerney, TL;Dimmock, NJ

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控制大流行性人类免疫缺陷病毒1型(HIV-1)感染理想地需要特定的粘膜免疫来保护生殖器区域,传播更经常通过这些区域发生。因此,一种能够刺激弥散性粘膜和全身保护性免疫反应的疫苗将是非常有用的。本文研究了一种嵌合植物病毒,豌豆花叶病毒(CPMV),表达HIV-1 IIIB (CPMV- hiv /1)跨膜gp41蛋白的22个氨基酸肽(残基731-752),在鼻或口服免疫后与广泛使用的粘膜佐剂霍乱毒素一起刺激HIV-1特异性和CPMV特异性粘膜和血清抗体的能力。cppv - hiv /1先前已被证明可通过肠外免疫刺激小鼠体内hiv - 1特异性血清抗体。所有小鼠经鼻内接种两剂10 μ g CPMV-HIV/1,在粪便中产生hiv - 1特异性IgA,以及更高水平的特异性血清抗体,主要是IgG2a。因此,主要是辅助性T 1细胞应答。所有小鼠也对CPMV表位有强烈反应。嵌合豇豆花叶病毒的口服免疫效果较差,即使剂量为500 μ g或更大,并且仅在少数小鼠中刺激hiv -1特异性血清抗体,并且没有粪便hiv -1特异性IgA。(C) 1998 Elsevier Science B.V.版权所有
Control of pandemic human immunodeficiency virus type 1 (HIV-1) infection ideally requires specific mucosal immunity to protect the genital regions through which transmission more often occurs. Thus a vaccine that stimulates a disseminated mucosal and systemic protective immune response would be extremely useful. Here we have investigated the ability of a chimeric plant virus, cowpea mosaic virus (CPMV), expressing a 22 aminoacid peptide (residues 731-752) of the transmembrane gp41 protein of HIV-1 IIIB (CPMV-HIV/1), to stimulate HIV-l-specific and CPMV-specific mucosal and serum antibody following intranasal or oral immunization together with the widely used mucosal adjuvant, cholera toxin. CPMV-HIV/1 has been shown previously to stimulate HIV-l-specific serum antibody in mice by parenteral immunization. All mice immunized intranasally with two doses of 10 mu g of CPMV-HIV/1 produced both HIV-l-specific IgA in faeces as well as higher levels of specific, predominantly IgG2a, serum antibody. Thus there was a predominantly T helper 1 cell response. All mice also responded strongly to CPMV epitopes. Oral immunization of the chimeric cowpea mosaic virus was less effective, even at doses of 500 mu g or greater, and stimulated HIV-1-specific serum antibody in only a minority of mice, and no faecal HIV-I specific IgA. (C) 1998 Elsevier Science B.V. All rights reserved.