Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers.

Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers.
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DOI:
10.1371/journal.pone.0033736
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Lewis DJ
Lewis DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huo Z;Bissett SL;Giemza R;Beddows S;Oeser C;Lewis DJ

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舌下途径已被提议作为诱导针对病毒感染的全身和粘膜免疫保护的无针选择。在对舌下或全身给予的病毒抗原的全身和粘膜体液免疫应答的转化研究中,18名年龄在19-31岁的健康女性志愿者在0、4和16周接受了四价人乳头瘤病毒疫苗的三次免疫接种,作为舌下滴剂(SL,n = 12)或肌内注射(IM,n = 6)。    IM抗原递送诱导或增强HPV特异性血清IgG和假病毒中和抗体,HPV特异性宫颈和阴道IgG,并引起循环IgG和伊加抗体分泌细胞。与IM递送相比,SL抗原诱导的血清IgG低1.38倍,宫颈/阴道IgG低1.22倍,并且仅在3/12名受试者中诱导或增强血清病毒中和抗体。这两种途径都不能重复诱导HPV特异性粘膜伊加。将需要替代的递送系统和佐剂来增强和评估人类舌下免疫后的免疫应答。 ClinicalTrials.gov NCT00949572
The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19–31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12) or intramuscular injection (IM, n = 6). IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ∼38-fold lower serum and ∼2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans. ClinicalTrials.gov NCT00949572
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