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Broadly neutralizing antibodies

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https://www.readbyqxmd.com/read/29343576/increased-epitope-complexity-correlated-with-antibody-affinity-maturation-and-a-novel-binding-mode-revealed-by-structures-of-rabbit-antibodies-against-the-third-variable-loop-v3-of-hiv-1-gp120
#1
Ruimin Pan, Yali Qin, Marisa Banasik, William Lees, Adrian J Shepherd, Michael W Cho, Xiang-Peng Kong
The V3 loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing antibodies (nAbs). Despite limited breadth, better characterization of the structural details of the interactions between these nAbs and their target epitopes would enhance our understanding of the mechanism of neutralization and facilitate designing better immunogens to induce nAbs with greater breadth. Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (mAbs), 10A3 and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343432/hiv-immunogens-affinity-is-key
#2
Savit Prabhu, Ian A Cockburn, Carola G Vinuesa
Generation of broadly neutralizing antibodies is a key aim of HIV vaccine design, but the precursor B cells are rare. Abbott et al. (2018) report that high affinity and avidity immunogens are required to promote maturation of low frequency B cells in germinal centers.
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29339724/granulocyte-colony-stimulating-factor-controls-neural-and-behavioral-plasticity-in-response-to-cocaine
#3
Erin S Calipari, Arthur Godino, Emily G Peck, Marine Salery, Nicholas L Mervosh, Joseph A Landry, Scott J Russo, Yasmin L Hurd, Eric J Nestler, Drew D Kiraly
Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#4
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29323105/enterovirus-d68-virus-like-particles-expressed-in-pichia-pastoris-potently-induce-neutralizing-antibody-responses-and-confer-protection-against-lethal-viral-infection-in-mice
#5
Chao Zhang, Xueyang Zhang, Wei Zhang, Wenlong Dai, Jing Xie, Liping Ye, Hongli Wang, Huan Chen, Qingwei Liu, Sitang Gong, Lanlan Geng, Zhong Huang
Enterovirus D68 (EV-D68) has been increasingly associated with severe respiratory illness and neurological complications in children worldwide. However, no vaccine is currently available to prevent EV-D68 infection. In the present study, we investigated the possibility of developing a virus-like particle (VLP)-based EV-D68 vaccine. We found that co-expression of the P1 precursor and 3CD protease of EV-D68 in Pichia pastoris yeast resulted in the generation of EV-D68 VLPs, which were composed of processed VP0, VP1, and VP3 capsid proteins and were visualized as ~30 nm spherical particles...
January 10, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29321310/therapeutic-efficacy-of-vectored-pgt121-gene-delivery-in-hiv-1-infected-humanized-mice
#6
Alexander Badamchi-Zadeh, Lawrence J Tartaglia, Peter Abbink, Christine A Bricault, Po-Ting Liu, Michael Boyd, Marinela Kirilova, Noe B Mercado, Ovini S Nanayakkara, Vladimir D Vrbanac, Andrew M Tager, Rafael A Larocca, Michael S Seaman, Dan H Barouch
Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1 specific bNAb PGT121 in wildtype and immunocompromised C57Bl/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29315059/multi-envelope-hiv-1-vaccine-development-two-targeted-immune-pathways-one-desired-protective-outcome
#7
Julia L Hurwitz, Mattia Bonsignori
In 2016, there were more than 30 million individuals living with HIV-1, ∼1.8 million new HIV-1 infections, and ∼1 million HIV-1-related deaths according to UNAIDS ( unaids.org ). Hence, a preventive HIV-1 vaccine remains a global priority. The variant envelopes of HIV-1 present a significant obstacle to vaccine development and the vaccine field has realized that immunization with a single HIV-1 envelope protein will not be sufficient to generate broadly neutralizing antibodies. Here we describe two nonmutually exclusive, targeted pathways with which a multi-envelope HIV-1 vaccine may generate protective immune responses against variant HIV-1...
January 9, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29311326/fitness-landscape-of-the-human-immunodeficiency-virus-envelope-protein-that-is-targeted-by-antibodies
#8
Raymond H Y Louie, Kevin J Kaczorowski, John P Barton, Arup K Chakraborty, Matthew R McKay
HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge is the design of immunogens and vaccination protocols that can elicit bnAbs that target regions of the virus's spike proteins where the likelihood of mutational escape is low due to the high fitness cost of mutations...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29295514/broadening-the-h5n3-vaccine-immunogenicity-against-h5n1-virus-by-modification-of-neutralizing-epitopes
#9
Subaschandrabose Rajesh Kumar, Sharenya Chelvaretnam, Yunrui Tan, Mookkan Prabakaran
The highly pathogenic avian influenza (HPAI) H5N1 virus remains to be one of the world's largest pandemic threats due to the emergence of new variants. The rapid evolution of new sub-lineages is currently the greatest challenge in vaccine development. In this study, we developed an epitope modified non-pathogenic H5N3 (A/duck/Singapore/97) vaccine for broad protection against influenza H5 subtype. H5N3 hemagglutinin (HA) mutant reassortant viruses with A/Puerto Rico/8/34 (PR8) backbone were generated by mutating amino acids at the 140th loop and 190th α-helix of hemagglutinin...
December 23, 2017: Viruses
https://www.readbyqxmd.com/read/29282882/recent-progress-in-immune-based-interventions-to-prevent-hiv-1-transmission-to-children
#10
Yegor Voronin, Ilesh Jani, Barney S Graham, Coleen K Cunningham, Lynne M Mofenson, Philippa M Musoke, Sallie R Permar, Gabriella Scarlatti
Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches...
December 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29281818/vaccine-induction-of-heterologous-tier-2-hiv-1-neutralizing-antibodies-in-animal-models
#11
Kevin O Saunders, Laurent K Verkoczy, Chuancang Jiang, Jinsong Zhang, Robert Parks, Haiyan Chen, Max Housman, Hilary Bouton-Verville, Xiaoying Shen, Ashley M Trama, Richard Scearce, Laura Sutherland, Sampa Santra, Amanda Newman, Amanda Eaton, Kai Xu, Ivelin S Georgiev, M Gordon Joyce, Georgia D Tomaras, Mattia Bonsignori, Steven G Reed, Andres Salazar, John R Mascola, M Anthony Moody, Derek W Cain, Mireille Centlivre, Sandra Zurawski, Gerard Zurawski, Harold P Erickson, Peter D Kwong, S Munir Alam, Yves Levy, David C Montefiori, Barton F Haynes
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29277486/development-of-a-high-throughput-bead-based-assay-system-to-measure-hiv-1-specific-immune-signatures-in-clinical-samples
#12
Thomas Liechti, Claus Kadelka, Hanna Ebner, Nikolas Friedrich, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola
The monitoring and assessment of a broadly neutralizing antibody (bnAb) based HIV-1 vaccine require detailed measurements of HIV-1 binding antibody responses to support the detection of correlates of protection. Here we describe the development of a flexible, high-throughput microsphere based multiplex assay system that allows monitoring complex binding antibody signatures. Studying a panel of 13 HIV-1 antigens in a parallel assessment of different IgG subclasses (IgG1, IgG2 and IgG3) we demonstrate the potential of our strategy...
December 22, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29274699/hiv-1-superinfection-can-occur-in-the-presence-of-broadly-neutralizing-antibodies
#13
Jennifer Serwanga, Deogratius Ssemwanga, Michael Muganga, Ritah Nakiboneka, Susan Nakubulwa, Sylvia Kiwuwa-Muyingo, Lynn Morris, Andrew D Redd, Thomas C Quinn, Pontiano Kaleebu
BACKGROUND: Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. METHODS: Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma...
December 20, 2017: Vaccine
https://www.readbyqxmd.com/read/29261802/two-classes-of-protective-antibodies-against-pseudorabies-virus-variant-glycoprotein-b-implications-for-vaccine-design
#14
Xiangdong Li, Fanli Yang, Xule Hu, Feifei Tan, Jianxun Qi, Ruchao Peng, Min Wang, Yan Chai, Liying Hao, Junhua Deng, Chenyu Bai, Juan Wang, Hao Song, Shuguang Tan, Guangwen Lu, George F Gao, Yi Shi, Kegong Tian
Pseudorabies virus (PRV) belongs to the Herpesviridae family, and is an important veterinary pathogen. Highly pathogenic PRV variants have caused severe epidemics in China since 2011, causing huge economic losses. To tackle the epidemics, we identified a panel of mouse monoclonal antibodies (mAbs) against PRV glycoprotein B (gB) that effectively block PRV infection. Among these 15 mAbs, fourteen of them block PRV entry in a complement-dependent manner. The remaining one, 1H1 mAb, however can directly neutralize the virus independent of complement and displays broad-spectrum neutralizing activities...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29261658/syn023-a-novel-humanized-monoclonal-antibody-cocktail-for-post-exposure-prophylaxis-of-rabies
#15
Tzu-Yuan Chao, Shiqi Ren, Enyun Shen, Susan Moore, Shou-Feng Zhang, Li Chen, Charles E Rupprecht, Eric Tsao
Rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (PEP). However, current PEP relies on polyclonal immune globulin products purified from pooled human (HRIG) or equine (ERIG) plasma that are either in chronic shortage or in association with safety concerns. Here, we present the development of an antibody cocktail, SYN023, made of two novel monoclonal antibodies (MAb) CTB011 and CTB012 that could serve as safer and more cost-effective alternatives to the current RIG products...
December 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29250072/alterations-in-b-cell-compartment-correlate-with-poor-neutralization-response-and-disease-progression-in-hiv-1-infected-children
#16
Heena Aggarwal, Lubina Khan, Omkar Chaudhary, Sanjeev Kumar, Muzamil Ashraf Makhdoomi, Ravinder Singh, Kanika Sharma, Nitesh Mishra, Rakesh Lodha, Maddur Srinivas, Bimal Kumar Das, Sushil Kumar Kabra, Kalpana Luthra
Several B cell defects are reported in HIV-1 infected individuals including variation in B cell subsets, polyclonal B cell activation and exhaustion, with broadly neutralizing antibodies elicited in less than 10-20% of the infected population. HIV-1 disease progression is faster in children than adults. B Lymphocyte Stimulator (BLyS), expressed on dendritic cells (DCs), is a key regulator of B cell homeostasis. Understanding how DCs influence B cell phenotype and functionality (viral neutralization), thereby HIV-1 disease outcome in infected children, is important to develop interventional strategies for restoration of B cell function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29249314/protective-effect-of-a-polyvalent-influenza-dna-vaccine-in-pigs
#17
Ingrid Karlsson, Marie Borggren, Maiken Worsøe Rosenstierne, Ramona Trebbien, James A Williams, Enric Vidal, Júlia Vergara-Alert, David Solanes Foz, Ayub Darji, Marta Sisteré-Oró, Joaquim Segalés, Jens Nielsen, Anders Fomsgaard
BACKGROUND: Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle-free delivery method, we have recently demonstrated a polyvalent influenza DNA vaccine that induces a broad immune response, including both humoral and cellular immunity. OBJECTIVES: To investigate the protection of our polyvalent influenza DNA vaccine approach in a pig challenge study...
January 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29248585/human-protective-monoclonal-antibodies-against-the-ha-stem-of-group-2-has-derived-from-an-h3n2-virus-infected-human
#18
Seiya Yamayoshi, Mutsumi Ito, Ryuta Uraki, Tadahiro Sasaki, Kazuyoshi Ikuta, Yoshihiro Kawaoka
OBJECTIVES: Broadly reactive human monoclonal antibodies against the HA stem of influenza A virus are being developed as therapeutic agents as well as to understand the epitopes that are essential for a universal influenza virus vaccine. METHODS: We isolated and characterized two hetero-reactive human monoclonal antibodies from an H3N2 virus-infected human. RESULTS: These antibodies, which are predominantly bound to the HA stem of group 2 HAs, used IGHV3-66 and IGHV4-38-2 germline genes, respectively...
December 14, 2017: Journal of Infection
https://www.readbyqxmd.com/read/29241550/structural-determination-of-the-broadly-reactive-anti-ighv1-69-anti-idiotypic-antibody-g6-and-its-idiotope
#19
Yuval Avnir, Kristina L Prachanronarong, Zhen Zhang, Shurong Hou, Eric C Peterson, Jianhua Sui, Hatem Zayed, Vinodh B Kurella, Andrew T McGuire, Leonidas Stamatatos, Brendan J Hilbert, Markus-Frederik Bohn, Timothy F Kowalik, Jeffrey D Jensen, Robert W Finberg, Jennifer P Wang, Margaret Goodall, Roy Jefferis, Quan Zhu, Nese Kurt Yilmaz, Celia A Schiffer, Wayne A Marasco
The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29239895/development-of-broad-neutralization-activity-in-shiv-infected-rhesus-macaques-after-long-term-infection
#20
Nan Gao, Wei Wang, Chu Wang, Tiejun Gu, Rui Guo, Bin Yu, Wei Kong, Chuan Qin, Elena E Giorgi, Zhiwei Chen, Samantha Townsley, Shiu-Lok Hu, Xianghui Yu, Feng Gao
OBJECTIVE: Non-human primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 Env vaccines. However, whether broadly neutralizing antibodies (bnAbs) can be elicited in NHPs infected with simian/human immunodeficiency virus (SHIV) has not been fully understood. The objective of this study is to investigate whether broad neutralization activities were developed in SHIV-infected macaques after long-term infection as in humans. DESIGN: Neutralization breadth and specificities in plasmas from SHIV-infected macaques could be determined by analyzing a panel of tier 2 viruses and their mutants...
December 12, 2017: AIDS
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