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Broadly neutralizing antibodies

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https://www.readbyqxmd.com/read/29166592/hiv-envelope-glycoform-heterogeneity-and-localized-diversity-govern-the-initiation-and-maturation-of-a-v2-apex-broadly-neutralizing-antibody-lineage
#1
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166578/glycans-function-as-anchors-for-antibodies-and-help-drive-hiv-broadly-neutralizing-antibody-development
#2
Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S Shivatare, Bryan Briney, James E Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R Burton
No abstract text is available yet for this article.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29163465/b-cell-activating-factor-and-the-b-cell-compartment-in-hiv-siv-infection
#3
REVIEW
Gwenoline Borhis, Maria Trovato, Nada Chaoul, Hany M Ibrahim, Yolande Richard
With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162799/structure-based-design-of-native-like-hiv-1-envelope-trimers-to-silence-non-neutralizing-epitopes-and-eliminate-cd4-binding
#4
Daniel W Kulp, Jon M Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R Willis, Michael Kubitz, Yumiko Adachi, Samantha M Reiss, Mia Shin, Natalia de Val, Andrew B Ward, Shane Crotty, Dennis R Burton, William R Schief
Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162391/impact-of-hiv-1-envelope-conformation-on-adcc-responses
#5
REVIEW
Jonathan Richard, Jérémie Prévost, Nirmin Alsahafi, Shilei Ding, Andrés Finzi
HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a 'closed' conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate 'partially open' (State 2) and then into the 'open' CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC)...
November 18, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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