A recombinant live attenuated measles vaccine vector primes effective HLA-A0201-restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against HIV-1 conserved epitopes.
A recombinant live attenuated measles vaccine vector primes effective HLA-A0201-restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against HIV-1 conserved epitopes.
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重组麻疹减毒活疫苗载体可引发有效的 HLA-A0201 限制性细胞毒性 T 淋巴细胞和针对 HIV-1 保守表位的广泛中和抗体。
DOI：
10.1016/j.vaccine.2005.04.024
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发表时间：
2005
期刊：
影响因子：
5.5
通讯作者：
Tangy,Frédéric
中科院分区：
文献类型：
--
作者：
Lorin,Clarisse;Delebecque,Frédéric;Labrousse,Valérie;DaSilva,Lucie;Lemonnier,François;Brahic,Michel;Tangy,Frédéric
麻疹减毒活疫苗（MV）可为儿童提供一种安全、有效的麻疹和人类免疫缺陷病毒1型（HIV-1）联合免疫接种载体。为了评价来源于经认证的施瓦茨麻疹疫苗（MVSchw）的载体引发有效的细胞毒性T细胞（CTL）和针对HIV-1保守表位的广泛中和抗体的能力，我们产生了表达HIV-1抗原的重组MVSchw病毒。我们证明，表达HIV-1衍生的CTL多表位的重组MVSchw病毒引发有效的HLA-A0201限制性CTL对多个保守的HIV-1表位在小鼠麻疹易感和人源化的主要组织相容性复合体（MHC）I类分子HLA-A0201。此外，我们发现，表达HIV-189.6gp140糖蛋白的重组MVSchw病毒，其高变V1，V2和V3环被删除（Δ V1 V2 V3 gp 140），诱导针对HIV-1原代分离株的广泛中和抗体。这些结果表明MVSchw儿科疫苗接种载体诱导有效的细胞和体液HIV特异性免疫应答。
Live attenuated measles vaccine (MV) could provide a safe and efficient pediatric vaccination vector to immunize children simultaneously against measles and human immunodeficiency virus type 1 (HIV-1). To evaluate the capacity of a vector derived from the certified Schwarz measles vaccine (MVSchw) to prime effective cytotoxic T cells (CTL) and broad neutralizing antibodies against HIV-1 conserved epitopes, we generated recombinant MVSchw viruses expressing HIV-1 antigens. We demonstrate that a recombinant MVSchw virus expressing an HIV-1-derived CTL polyepitope primes effective HLA-A0201-restricted CTLs against multiple conserved HIV-1 epitopes in mice susceptible to measles and humanized for the major histocompatibility complex (MHC) class-I molecule HLA-A0201. Additionally, we show that a recombinant MVSchw virus expressing an HIV-189.6gp140 glycoprotein whose hyper variable V1, V2 and V3 loops were deleted (ΔV1V2V3gp140), induces broadly neutralizing antibodies against HIV-1 primary isolates. These results show that the MVSchw pediatric vaccination vector induces efficient cellular and humoral HIV-specific immune responses.