Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers.,Immunity

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Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers.
Immunity ( IF 32.4 ) Pub Date : 2018-12-11 , DOI: 10.1016/j.immuni.2018.11.011
Matthias G Pauthner ₁ , Joseph P Nkolola ₂ , Colin Havenar-Daughton ₃ , Ben Murrell ₄ , Samantha M Reiss ₃ , Raiza Bastidas ₁ , Jérémie Prévost ₅ , Rebecca Nedellec ₁ , Benjamin von Bredow ₆ , Peter Abbink ₂ , Christopher A Cottrell ₇ , Daniel W Kulp ₈ , Talar Tokatlian ₉ , Bartek Nogal ₇ , Matteo Bianchi ₁ , Hui Li ₁₀ , Jeong Hyun Lee ₃ , Salvatore T Butera ₁₁ , David T Evans ₆ , Lars Hangartner ₁ , Andrés Finzi ₁₂ , Ian A Wilson ₇ , Richard T Wyatt ₁ , Darrell J Irvine ₁₃ , William R Schief ₁ , Andrew B Ward ₇ , Rogier W Sanders ₁₄ , Shane Crotty ₁₅ , George M Shaw ₁₀ , Dan H Barouch ₁₆ , Dennis R Burton ₁₇

Affiliation

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.
Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA.
Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Departments of Biological Engineering and Materials Science & Engineering, MIT, Cambridge, MA 02139, USA.
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

中文翻译：

在非人类灵长类动物中从疫苗诱导的同源2 SHIV攻击的保护取决于血清中和抗体滴度。

艾滋病毒中和抗体（nAbs）的被动给药可以保护猕猴免受难以中和的2级嵌合猿猴-人免疫缺陷病毒（SHIV）攻击。但是，尚未建立疫苗接种后nAb介导的保护的条件。在这里，我们从总共78只用重组天然样（SOSIP）Env三聚体免疫的动物中选择了6个具有高或低血清nAb滴度的恒河猴。用同源2级SHIVBG505重复直肠内攻击导致未免疫和低滴度动物迅速感染。但是，高滴度动物表现出的保护作用随着nAb效价的逐渐下降而逐渐丧失。自身血清ID50 nAb滴度约为1：500，可提供90％以上的中等剂量SHIV感染防护。相比之下，抗体依赖性细胞的细胞毒性和T细胞活性与保护作用无关。因此，基于Env蛋白的疫苗接种策略可通过诱导2 nAbs来防止恒河猴猕猴中难于中和的SHIV攻击，前提是可以达到并维持适当的中和效价。

更新日期：2018-12-11

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