Ex vivo production of autologous whole inactivated HIV-1 for clinical use in therapeutic vaccines

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• 作者：Cristina Gil^a ; ^{cgil@clinic.ub.es"" rel=""nofollow} ; Nú ; ria Climent^a ; Felipe Garc&#xed ; a^a ; ^b ; Carmen Hurtado^a ; Sara Nieto-Má ; rquez^a ; Agathe Leó ; n^a ; M Teresa Garc&#xed ; a^a ; Cristina Rovira^a ; Laia Miralles^a ; Judith Dalmau^e ; Tomá ; s Pumarola^c ; Manel Almela^c ; Javier Martinez-Picado^e ; ^f ; Jeffrey D. Lifson^g ; Laura Zamora^a ; José ; M. Miró ; ^a ; ^b ; Christian Brander^e ; ^f ; Bonaventura Clotet^e ; Teresa Gallart^a ; ^d ; José ; M. Gatell^a ; ^b
• 关键词：Autologous HIV-1 immunogen ; Heat inactivated HIV-1 ; Therapeutic vaccine
• 刊名：Vaccine
• 出版年：2011
• 出版时间：5 August 2011
• 年：2011
• 卷：29
• 期：34
• 页码：5711-5724
• 全文大小：1689 K

文摘

This study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated HIV-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic HIV-1 vaccine (Clinical Trial DCV-2, NCT00402142). For each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing CD4-enriched PBMCs from the HIV-1-infected patient with PBMC from HIV-seronegative unrelated healthy volunteer donors. The viral supernatants were heat-inactivated and concentrated to obtain 1 mL of autologous immunogen, which was used to load autologous dendritic cells of each patient. High sequence homology was found between the inactivated virus immunogen and the HIV-1 circulating in plasma at the time of HIV-1 isolation. Immunogens contained up to 10⁹ HIV-1 RNA copies/mL showed considerably reduced infectivity after heat inactivation (median of 5.6 log₁₀), and were free of specified adventitious agents. The production of individualized lots of immunogen based on autologous inactivated HIV-1 virus fulfilling clinical-grade good manufacturing practice proved to be feasible, consistent with predetermined specifications, and safe for use in a clinical trial designed to test autologous dendritic cell-based therapeutic HIV-1 vaccine.