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使用多种痘病毒载体对恒河猴进行异源初免/加强免疫。

Heterologous prime/boost immunization of rhesus monkeys by using diverse poxvirus vectors.

作者信息

Santra Sampa, Sun Yue, Parvani Jenny G, Philippon Valerie, Wyand Michael S, Manson Kelledy, Gomez-Yafal Alicia, Mazzara Gail, Panicali Dennis, Markham Phillip D, Montefiori David C, Letvin Norman L

机构信息

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

J Virol. 2007 Aug;81(16):8563-70. doi: 10.1128/JVI.00744-07. Epub 2007 Jun 6.

Abstract

As the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. The present study was initiated to explore the use of divergent pox vectors in a prime/boost regimen to elicit high-frequency cellular immune responses to human immunodeficiency virus type 1 envelope and simian immunodeficiency virus gag in rhesus monkeys. We demonstrated that monkeys vaccinated with a recombinant modified vaccinia virus Ankara (rMVA) prime/recombinant fowlpox virus (rFPV) boost regimen and monkeys vaccinated with a recombinant vaccinia virus prime/rFPV boost regimen developed comparable cellular immune responses that were greater in magnitude than those elicited by a homologous prime/boost with rMVA. Nevertheless, comparable magnitude recall cellular immune responses were observed in monkeys vaccinated with heterologous and homologous recombinant poxvirus following challenge with the CXCR4-tropic SHIV-89.6P. Consistent with this finding, comparable levels of containment of viral replication and CD4(+) T-lymphocyte preservation were seen in these groups of recombinant poxvirus-vaccinated monkeys. This study supports further exploration of combining recombinant vectors of the same family in prime/boost immunization strategies to optimize vaccine-elicited cellular immune responses.

摘要

随着某些类型载体中潜在免疫原多样性的增加,使用同一家族载体的不同成员进行异源初免/加强免疫的可能性应运而生。本研究旨在探索在初免/加强免疫方案中使用不同的痘病毒载体,以在恒河猴中引发针对1型人类免疫缺陷病毒包膜和猿猴免疫缺陷病毒gag的高频细胞免疫反应。我们证明,接种重组安卡拉痘苗病毒(rMVA)初免/重组禽痘病毒(rFPV)加强免疫方案的猴子以及接种重组痘苗病毒初免/rFPV加强免疫方案的猴子产生了相当的细胞免疫反应,其强度大于rMVA同源初免/加强免疫所引发的反应。然而,在用CXCR4嗜性的SHIV-89.6P攻击后,接种异源和同源重组痘病毒的猴子中观察到了相当强度的回忆细胞免疫反应。与此发现一致,在这些重组痘病毒接种的猴子组中,病毒复制的抑制水平和CD4(+) T淋巴细胞的保存情况相当。本研究支持进一步探索在初免/加强免疫策略中组合同一家族的重组载体,以优化疫苗引发的细胞免疫反应。

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