Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina
Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina
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DOI：
10.1128/iai.65.7.2676-2684.1997
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发表时间：
1997-07-01
影响因子：
3.1
通讯作者：
Rudin, A
中科院分区：
文献类型：
--
作者：
Bergquist, C;Johansson, EL;Rudin, A
45名志愿者接受了10、100或1000毫克霍乱毒素B亚单位(CTB)的两次鼻腔接种。分别于二免前和二免后1周采血、鼻腔和阴道分泌物，用酶联免疫吸附试验检测特异性和总胆固醇(TC)、总免疫球蛋白A(IgA)和免疫球蛋白G(Ig G)效价。分别于接种后6个月(n=16)和1年(n=14)采集样本。志愿者对10和100微克的剂量耐受性良好，但1000微克的剂量会导致鼻腔分泌物增加，并导致数小时的反复打喷嚏。中剂量免疫后1周，CTB特异性血清IgA和Ig G分别增加21倍和7倍，高剂量后分别增加61倍和37倍。鼻腔分泌物中，中剂量后特异性IgA和IgE分别增加2倍和6倍，高剂量后分别增加2倍和20倍。阴道分泌物中，中剂量后特异性IgA和IgG分别增加3倍和5倍，高剂量后分别增加56倍和74倍。最低剂量未引起血清或分泌物抗体滴度显著升高，免疫后6个月分泌物中特异性Ig A和Ig G水平仍有升高，但1年后有所下降。这些结果表明，鼻腔接种CTB可诱导强烈的系统和粘膜抗体反应，提示CTB可作为抗原的载体，诱导对全身以及呼吸道和生殖器感染的保护性免疫。
Forty-five volunteers were vaccinated twice intranasally with 10, 100, or 1,000 mu g of cholera toxin B subunit (CTB). Blood and nasal and vaginal secretions were collected before and 1 week after the second vaccination from ail volunteers, and the specific and tc,tal immunoglobulin A (IgA) and IgG titers were determined by enzyme-linked immunosorbent assay. Samples were also taken 6 months (n = 16) and 1 year (n = 14) after the vaccination. The 10- and 100-mu g doses were well tolerated by the volunteers, but the 1,000-mu g dose induced increased secretions from the nose and repetitive sneezings for several hours. The CTB-specific serum IgA and IgG increased 21- and 7-fold, respectively, 1 week after vaccination with the medium dose and increased 61- and 37-fold, respectively, after the high dose. In nasal secretions the specific IgA and Ige increased 2- and 6-fold after the medium dose and 2- and 20-fold after the high dose, respectively. In vaginal secretions the specific IgA and IgG increased 3 and 5-fold after the medium dose and 56- and 74-fold after the high dose, respectively. The lowest dose did not induce ang significant antibody titer increases in serum or in secretions, The specific IgA and IgG levels in secretions were still elevated after 6 months but were decreasing 1 year after the vaccination. These results show that intranasal vaccination of humans with CTB induces strong systemic and mucosal antibody responses and suggest that CTB mag be used as a carrier for antigens that induce protective immunity against systemic as well as respiratory and genital infections.