IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells

在非人灵长类动物中,IDLV-HIV-1 Env 疫苗接种可诱导抗原特异性记忆 B 细胞的亲和力成熟。

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作者:Maria Blasi ,Donatella Negri ,Celia LaBranche ,S Munir Alam ,Erich J Baker ,Elizabeth C Brunner ,Morgan A Gladden ,Zuleika Michelini ,Nathan A Vandergrift ,Kevin J Wiehe ,Robert Parks ,Xiaoying Shen ,Mattia Bonsignori ,Georgia D Tomaras ,Guido Ferrari ,David C Montefiori ,Sampa Santra ,Barton F Haynes ,Michael A Moody ,Andrea Cara ,Mary E Klotman

Abstract

HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We showed previously that a single immunization with a SIV-based integrase-defective lentiviral vector (IDLV) expressing the 1086.C HIV-1-envelope induced durable, high-magnitude immune responses in non-human primates (NHPs). In this study, we have further characterized the humoral responses by assessing antibody affinity maturation and antigen-specific memory B-cell persistence in two vaccinated macaques. These animals were also boosted with IDLV expressing the heterologous 1176.C HIV-1-Env to determine if neutralization breadth could be increased, followed by evaluation of the injection sites to assess IDLV persistence. IDLV-Env immunization was associated with persistence of the vector DNA for up to 6 months post immunization and affinity maturation of antigen-specific memory B cells.

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