作者: Briney, Bryan ; Ozorowski, Gabriel ; Sesterhenn, Fabian ; Ray, Rashmi ; Cottrell, Christopher A ; Cheng, Hwei-Ling ; Saha, Swati ; Diedrich, Jolene K ; Lee, Chang-Chun D ; Georgeson, Erik ; Wang, Xuesong ; Phung, Ivy ; Kulp, Daniel W ; Skog, Patrick D ; Marina-Zárate, Ester ; Ward, Andrew B ; Ruiz, Jennifer ; Elsliger, Marc A ; McKenney, Katherine ; Lee, Jeong Hyun ; Huang, Jiachen ; Zhou, Xiaoya ; Hu, Xiaozhen ; Eskandarzadeh, Saman ; Wilson, Ian A ; Silvestri, Guido ; Flynn, Claudia T ; Kubitz, Michael ; Landais, Elise ; Batista, Facundo D ; Liguori, Alessia ; Tingle, Ryan D ; Burton, Dennis R ; Baboo, Sabyasachi ; Adachi, Yumiko ; Sok, Devin ; Tian, Ming ; Grigoryan, Gevorg ; Paulson, James C ; Allen, Joel D ; Shields, Kaitlyn ; Smith, Melissa L ; Havenar-Daughton, Colin ; Pecetta, Simone ; Alt, Frederick W ; Schief, William R ; Yates, John R ; Davis, Jillian ; Toy, Laura ; Amara, Rama R ; Schiffner, Torben ; Lin, Ying-Cing ; Zhou, Jianfu ; Rodriguez, Oscar L ; Hurtado, Jonathan ; Swanson, Olivia ; Irimia, Adriana ; Carnathan, Diane G ; Kalyuzhniy, Oleksandr ; Himansu, Sunny ; Watson, Corey T ; Rantalainen, Kimmo ; Crotty, Shane ; Liang, Chi-Hui ; Lewis, Vanessa ; Cho, So Yeon ; Nair, Usha ; Kirsch, Kathrin H ; Spencer, Skye ; Phelps, Nicole ; Serra, Andreia M ; Schultze, Steven ; Crispin, Max ; Ngo, Julia T ; Willis, Jordan R

AbstractA key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

2023-11-01·Current Opinion in HIV and AIDS

Progress with induction of HIV broadly neutralizing antibodies in the Duke Consortia for HIV/AIDS Vaccine Development

Review

作者: Weissman, Drew ; Haynes, Barton F. ; Wiehe, Kevin ; Saunders, Kevin O. ; Alam, S. Munir

Purpose of reviewDesign of an HIV vaccine that can induce broadly neutralizing antibodies (bnAbs) is a major goal. However, HIV bnAbs are not readily made by the immune system. Rather HIV bnAbs are disfavored by a number of virus and host factors. The purpose of the review is to discuss recent progress made in the design and use of immunogens capable of inducing HIV bnAbs in the Duke Consortia for HIV/AIDS Vaccine Development.Recent findingsNew immunogens capable of binding with high affinity to unmutated common ancestors (UCAs) of bnAb B cell lineages have been designed and strategies for stabilization of HIV Env in its prefusion state are being developed. Success is starting to be translated from preclinical studies of UCA-targeting immunogens in animals, to success of initiating bnAb lineages in humans.SummaryRecent progress has been made in both immunogen design and in achieving bnAb B cell lineage induction in animal models and now in human clinical trials. With continued progress, a practical HIV/AIDS vaccine may be possible. However, host constraints on full bnAb maturation remain as potential roadblocks for full maturation of some types of bnAbs.

2023-09-01·Journal of virus eradication

To prescreen or not to prescreen for broadly neutralizing antibody sensitivity in HIV cure-related trials.

Article

作者: Dubé, Karine ; Patel, Hursch

The use of broadly neutralizing antibodies (bNAbs) as a cure-related research strategy for human immunodeficiency virus (HIV) has gained attention from the scientific community. bNAbs are specialized antibodies that target HIV-1 by binding to proteins on the surface of the virus, preventing the infection of human cells. In HIV-1 clinical studies assessing the use of bNAbs, it has been common practice to prescreen potential participants for bNAb sensitivity. However, the use of pre-screening in HIV-1 bNAb clinical trials is a topic of ongoing debate, with regard to its potential benefits and limitations. In this paper, we examine the possible benefits and limitations of pre-screening for bNAb sensitivity in HIV-1 cure-related studies, and suggest alternative methods which may be more effective or efficient at saving costs and time. Ultimately, the decision to use pre-screening in HIV-1 bNAb clinical trials should be based on a careful assessment of the potential benefits and limitations of this approach, as well as the specific needs, goals, design, and population of the study in question.

100 项与 Enhanced bnAbs for HIV prevention(International AIDS Vaccine Initiative) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床1期	美国	International AIDS Vaccine Initiative, Inc.	2022-09-01
HIV感染	临床前	美国	The Scripps Research Institute	2022-09-01
HIV感染	临床前	美国	Serum Institute of India Pvt Ltd.	2022-09-01
HIV感染	临床前	美国	University of Oslo	2022-09-01