Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan.,Immunity

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Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan.
Immunity ( IF 32.4 ) Pub Date : 2019-07-16 , DOI: 10.1016/j.immuni.2019.06.004
Jeffrey Umotoy ₁ , Bernard S Bagaya ₂ , Collin Joyce ₃ , Torben Schiffner ₄ , Sergey Menis ₁ , Karen L Saye-Francisco ₃ , Trevor Biddle ₃ , Sanjay Mohan ₅ , Thomas Vollbrecht ₅ , Oleksander Kalyuzhniy ₁ , Sharon Madzorera ₆ , Dale Kitchin ₆ , Bronwen Lambson ₆ , Molati Nonyane ₆ , William Kilembe ₇ , , , Pascal Poignard ₈ , William R Schief ₉ , Dennis R Burton ₁₀ , Ben Murrell ₁₁ , Penny L Moore ₁₂ , Bryan Briney ₄ , Devin Sok ₁₃ , Elise Landais ₁₄

Affiliation

International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, USA.
UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda; Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala-Uganda.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, 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.
Department of Medicine, University of California San Diego, San Diego, CA 92103, USA.
Centre for HIV and STIs, National Institute for Communicable Diseases, of the National Health Laboratory Service (NHLS), Johannesburg 2131, South Africa.
Rwanda-Zambia HIV Research Group, Lusaka & Ndola, Zambia.
International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Institut de Biologie Structurale, Université Grenoble Alpes, Commissariat a l'Energie Atomique, Centre National de Recherche Scientifique and Centre Hospitalier Universitaire Grenoble Alpes, 38044 Grenoble, France.
International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, 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.
International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, 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; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02114, USA.
Department of Medicine, University of California San Diego, San Diego, CA 92103, USA; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
Centre for HIV and STIs, National Institute for Communicable Diseases, of the National Health Laboratory Service (NHLS), Johannesburg 2131, South Africa; School of Pathology Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of Kwa-Zulu Natal, Durban 4013, South Africa.
International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, 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.
International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ∼24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.

中文翻译：

VRC01类HIV广泛中和的抗体谱系的快速集中成熟涉及N276-聚糖的结合和调节。

靶向HIV包膜CD4结合位点的VH1-2限制性VRC01类抗体是HIV疫苗策略的主要重点。然而，VRC01类抗体发育的详细分析受到自然感染过程中这些反应的罕见性以及缺乏此类反应的纵向采样的限制。为了指导疫苗策略，我们在感染亚型C的IAVI Protocol C中和剂PC063中绘制了VRC01类抗体谱系（PCIN63）的图谱。PCIN63单克隆抗体具有标志性的VRC01类特征，并显示出与原型VRC01抗体相似的中和广度，但突变少了2至3倍。在谱系出现后约24个月内迅速发生成熟，并且在关键接触残基上积累了体细胞超突变。

更新日期：2019-07-17

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