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Broad neutralizing antibody

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https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#1
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150603/bacterially-derived-synthetic-mimetics-of-mammalian-oligomannose-prime-antibody-responses-that-neutralize-hiv-infectivity
#2
Ralph Pantophlet, Nino Trattnig, Sasha Murrell, Naiomi Lu, Dennis Chau, Caitlin Rempel, Ian A Wilson, Paul Kosma
Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29139548/prospects-from-systems-serology-research
#3
REVIEW
Kelly B Arnold, Amy W Chung
Antibodies are highly functional glycoproteins capable of providing immune protection through multiple mechanisms, including direct pathogen neutralization and the engagement of their Fc-portions with surrounding effector immune cells and immune components that induce anti-pathogenic responses. Small modifications to multiple antibody biophysical features induced by vaccines and other therapeutic regimens can significantly alter functional immune outcomes, though it is difficult to predict which combinations confer protective immunity...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#4
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29136030/prospects-for-passive-immunity-to-prevent-hiv-infection
#5
Lynn Morris, Nonhlanhla N Mkhize
In a Perspective, Lynn Morris and Nonhlanhla Mkhize discuss the prospects for broadly neutralizing antibodies to be used in preventing HIV infection.
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135340/generation-and-testing-anti-influenza-human-monoclonal-antibodies-in-a-new-humanized-mouse-model-draga-hla-a2-hla-dr4-rag1-ko-il-2r%C3%AE-c-ko-nod
#6
Mirian Mendoza, Angela Ballesteros, Qiu Qi, Luis Pow Sang, Soumya Shashikumar, Sofia Casares, Teodor-D Brumeanu
Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rγc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb)...
November 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29118747/emerging-targets-for-developing-t-cell-mediated-vaccines-for-human-immunodeficiency-virus-hiv-1
#7
REVIEW
Danushka K Wijesundara, Charani Ranasinghe, Branka Grubor-Bauk, Eric J Gowans
Human immunodeficiency virus (HIV)-1 has infected >75 million individuals globally, and, according to the UN, is responsible for ~2.1 million new infections and 1.1 million deaths each year. Currently, there are ~37 million individuals with HIV infection and the epidemic has already resulted in 35 million deaths. Despite the advances of anti-retroviral therapy (ART), a cost-effective vaccine remains the best long-term solution to end the HIV-1 epidemic especially given that the vast majority of infected individuals live in poor socio-economic regions of the world such as Sub-Saharan Africa which limits their accessibility to ART...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29107699/synthetic-three-component-hiv-1-v3-glycopeptide-immunogens-induce-glycan-dependent-antibody-responses
#8
Hui Cai, Jared Orwenyo, John P Giddens, Qiang Yang, Roushu Zhang, Celia C LaBranche, David C Montefiori, Lai-Xi Wang
Eliciting broadly neutralizing antibody (bNAb) responses against HIV-1 is a major goal for a prophylactic HIV-1 vaccine. One approach is to design immunogens based on known broadly neutralizing epitopes. Here we report the design and synthesis of an HIV-1 glycopeptide immunogen derived from the V3 domain. We performed glycopeptide epitope mapping to determine the minimal glycopeptide sequence as the epitope of V3-glycan-specific bNAbs PGT128 and 10-1074. We further constructed a self-adjuvant three-component immunogen that consists of a 33-mer V3 glycopeptide epitope, a universal T helper epitope P30, and a lipopeptide (Pam3CSK4) that serves as a ligand of Toll-like receptor 2...
October 4, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29097089/anti-hiv-passive-immunization-new-weapons-in-the-arsenal
#9
Ruth M Ruprecht
Anti-HIV passive immunization with human neutralizing monoclonal antibodies (nmAbs) has made exciting gains: (i) identification of the HIV envelope V2 apex as a new in vivo protective epitope, (ii) a novel clade C SHIV for challenge studies, and (iii) a highly protective, trispecific nmAb. Potent, broad-spectrum protection by nmAbs holds promise.
October 30, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29095961/nanobodies-targeting-norovirus-capsid-reveal-functional-epitopes-and-potential-mechanisms-of-neutralization
#10
COMPARATIVE STUDY
Anna D Koromyslova, Grant S Hansman
Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29074219/a-novel-neutralizing-human-monoclonal-antibody-broadly-abrogates-hepatitis-c-virus-infection-in-vitro-and-in-vivo
#11
Isabelle Desombere, Ahmed Atef Mesalam, Richard A Urbanowicz, Freya Van Houtte, Lieven Verhoye, Zhen-Yong Keck, Ali Farhoudi, Koen Vercauteren, Karin E Weening, Thomas F Baumert, Arvind H Patel, Steven K H Foung, Jonathan Ball, Geert Leroux-Roels, Philip Meuleman
Infections with hepatitis C virus (HCV) represent a worldwide health burden and a prophylactic vaccine is still not available. Liver transplantation (LT) is often the only option for patients with HCV-induced end-stage liver disease. However, immediately after transplantation, the liver graft becomes infected by circulating virus, resulting in accelerated progression of liver disease. Although the efficacy of HCV treatment using direct-acting antivirals has improved significantly, immune compromised LT-patients and patients with advanced liver disease remain difficult to treat...
October 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29073897/a-comparative-study-of-multiple-clinical-enterovirus-71-isolates-and-evaluation-of-cross-protection-of-inactivated-vaccine-strain-fy-23%C3%A2-k-b-in-vitro
#12
Ting Yang, Hua Li, Lei Yue, Xia Song, Tianhong Xie, Shaohui Ma, Huaqing Meng, Ye Zhang, Xin He, Runxiang Long, Rong Yang, Fangyu Luo, Zhongping Xie, Qihan Li
BACKGROUND: Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease, which mostly affects infants and children and leads to severe neurological diseases. Vaccination offers the best option for disease control. We have screened the virus strain FY-23 K-B, which is used as an inactivated vaccine strain. An important issue in the development of vaccines is whether they provide cross protection against all other strains. METHODS: We collected and identified 19 clinical EV71 isolates from mainland China, which all belong to the C4 genotype...
October 26, 2017: Virology Journal
https://www.readbyqxmd.com/read/29071472/immune-interventions-to-eliminate-the-hiv-reservoir
#13
Denise C Hsu, Jintanat Ananworanich
Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV...
October 26, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29070688/structural-basis-for-the-escape-of-human-astrovirus-from-antibody-neutralization-broad-implications-for-rational-vaccine-design
#14
Walter A Bogdanoff, Edmundo I Perez, Tomás López, Carlos F Arias, Rebecca M DuBois
Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection, however antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (mAb PL-2)...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29065122/prediction-of-hiv-1-sensitivity-to-broadly-neutralizing-antibodies-shows-a-trend-towards-resistance-over-time
#15
Anna Hake, Nico Pfeifer
Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus...
October 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29062895/norovirus-escape-from-broadly-neutralizing-antibodies-is-limited-to-allostery-like-mechanisms
#16
Abimbola O Kolawole, Hong Q Smith, Sophia A Svoboda, Madeline S Lewis, Michael B Sherman, Gillian C Lynch, B Montgomery Pettitt, Thomas J Smith, Christiane E Wobus
Ideal antiviral vaccines elicit antibodies (Abs) with broad strain recognition that bind to regions that are difficult to mutate for escape. Using 10 murine norovirus (MNV) strains and 5 human norovirus (HuNoV) virus-like particles (VLPs), we identified monoclonal antibody (MAb) 2D3, which broadly neutralized all MNV strains tested. Importantly, escape mutants corresponding to this antibody were very slow to develop and were distal to those raised against our previously studied antibody, A6.2. To understand the atomic details of 2D3 neutralization, we determined the cryo-electron microscopy (cryo-EM) structure of the 2D3/MNV1 complex...
September 2017: MSphere
https://www.readbyqxmd.com/read/29062081/an-engineered-vaccine-of-the-plasmodium-vivax-duffy-binding-protein-enhances-induction-of-broadly-neutralizing-antibodies
#17
Francis B Ntumngia, Camilla V Pires, Samantha J Barnes, Miriam T George, Richard Thomson-Luque, Flora S Kano, Jessica R S Alves, Darya Urusova, Dhelio B Pereira, Niraj H Tolia, Christopher L King, Luzia H Carvalho, John H Adams
Plasmodium vivax invasion into human reticulocytes is a complex process. The Duffy binding protein (DBP) dimerization with its cognate receptor is vital for junction formation in the invasion process. Due to its functional importance, DBP is considered a prime vaccine candidate, but variation in B-cell epitopes at the dimer interface of DBP leads to induction of strain-limited immunity. We believe that the polymorphic residues tend to divert immune responses away from functionally conserved epitopes important for receptor binding or DBP dimerization...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29059230/a-structural-explanation-for-the-low-effectiveness-of-the-seasonal-influenza-h3n2-vaccine
#18
Nicholas C Wu, Seth J Zost, Andrew J Thompson, David Oyen, Corwin M Nycholat, Ryan McBride, James C Paulson, Scott E Hensley, Ian A Wilson
The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA) often arise during virus passaging that change its antigenicity and hence vaccine effectiveness. Here, we characterize the effect of a prevalent substitution, L194P, in egg-passaged H3N2 viruses...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29051495/the-%C3%AE-20-%C3%AE-21-of-gp120-is-a-regulatory-switch-for-hiv-1-env-conformational-transitions
#19
Alon Herschhorn, Christopher Gu, Francesca Moraca, Xiaochu Ma, Mark Farrell, Amos B Smith, Marie Pancera, Peter D Kwong, Arne Schön, Ernesto Freire, Cameron Abrams, Scott C Blanchard, Walther Mothes, Joseph G Sodroski
The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051051/brief-introduction-of-current-technologies-in-isolation-of-broadly-neutralizing-hiv-1-antibodies
#20
REVIEW
Zehua Sun, Lixin Yan, Jiansong Tang, Qian Qian, Jerica Lenberg, Dandan Zhu, Wan Liu, Kao Wu, Yilin Wang, Shiqiang Lu
HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed, passive immunization for prevention and treatment of HIV-1 infection may alleviate the burden caused by the pandemic. Among HIV-1 infected individuals, about 20% of them generated cross-reactive neutralizing antibodies two to four years after infection, the details of which could provide knowledge for effective vaccine design. Recent progress in techniques for isolation of human broadly neutralizing antibodies has facilitated the study of passive immunization...
October 16, 2017: Virus Research
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