Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection.

Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection.
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阳离子脂质/DNA复合物(JVRS-100)结合流感疫苗(Fluzone)增加了抗体反应,细胞免疫和抗原漂移的保护。

DOI:
10.1016/j.vaccine.2009.04.054
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发表时间:
2009-06-12
期刊:
影响因子:
5.5
通讯作者:
Fairman J
Fairman J
中科院分区:
医学3区
文献类型:
--
作者:
Lay M;Callejo B;Chang S;Hong DK;Lewis DB;Carroll TD;Matzinger S;Fritts L;Miller CJ;Warner JF;Liang L;Fairman J

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安全有效的流感疫苗佐剂可以提高中和抗体水平,包括针对漂移病毒亚型的中和抗体水平和T细胞免疫力,这将是疫苗设计的一个重大进展。JVRS-100佐剂由DOTIM/胆固醇阳离子脂质体-DNA复合物组成,特别适用于需要诱导高水平抗体和T细胞免疫的疫苗,包括CD 8+细胞毒性T淋巴细胞(CTL)。JVRS-100包含蛋白抗原导致诱导增强的体液和细胞介导的(即,CD 4+和CD 8 + T细胞)免疫应答。与单独接种Fluzone®相比,JVRS-100佐剂与裂解三价流感疫苗(Fluzone® - sanofi pasteur)组合在小鼠和非人灵长类动物中引起增加的抗体和T细胞应答。用JVRS-100-Fluzone®接种并用H1N1(PR/8/34)和流感B(B/Lee/40)病毒的抗原漂移株攻击的小鼠与无佐剂疫苗的接受者相比具有更高级别的保护,如通过体重减轻的减弱和存活率的增加所测量的。结果表明,JVRS-100佐剂显著增加了免疫原性,并使用现有流感疫苗保护免受漂移株攻击。
Safe and effective adjuvants for influenza vaccines that could increase both the levels of neutralizing antibody, including against drifted viral subtypes, and T-cell immunity would be a major advance in vaccine design. The JVRS-100 adjuvant, consisting of DOTIM/cholesterol cationic liposome-DNA complexes, is particularly promising for vaccines that require induction of high levels of antibody and T-cell immunity, including CD8+ cytotoxic T lymphocytes (CTL). Inclusion of protein antigens with JVRS-100 results in the induction of enhanced humoral and cell-mediated (i.e., CD4+, and CD8+ T cells) immune responses. The JVRS-100 adjuvant combined with a split trivalent influenza vaccine (Fluzone® - sanofi pasteur) elicited increased antibody and T-cell responses in mice and non-human primates compared to vaccination with Fluzone® alone. Mice vaccinated with JVRS-100-Fluzone® and challenged with antigenically drifted strains of H1N1 (PR/8/34) and influenza B (B/Lee/40) viruses had higher grade protection, as measured by attenuation of weight loss and increased survival, compared to recipients of unadjuvanted vaccine. The results indicate that the JVRS-100 adjuvant substantially increases immunogenicity and protection from drifted-strain challenge using an existing influenza vaccine.
在B淋巴细胞缺陷小鼠中对致命流感病毒感染的抗性和恢复。
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