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Broadly neutralizing antibody

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https://www.readbyqxmd.com/read/29677181/exploiting-glycan-topography-for-computational-design-of-env-glycoprotein-antigenicity
#1
Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B Karsten, Todd J Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L Brass, Michael Tiemeyer, Michael Seaman, John R Mascola, Lance Wells, Douglas A Lauffenburger, Galit Alter
Mounting evidence suggests that glycans, rather than merely serving as a "shield", contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity...
April 20, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29672607/infant-transmitted-founder-hiv-1-viruses-from-peripartum-transmission-are-neutralization-resistant-to-paired-maternal-plasma
#2
Amit Kumar, Claire E P Smith, Elena E Giorgi, Joshua Eudailey, David R Martinez, Karina Yusim, Ayooluwa O Douglas, Lisa Stamper, Erin McGuire, Celia C LaBranche, David C Montefiori, Genevieve G Fouda, Feng Gao, Sallie R Permar
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29671786/hiv-vaccination-a-roadmap-among-advancements-and-concerns
#3
REVIEW
Maria Trovato, Luciana D'Apice, Antonella Prisco, Piergiuseppe De Berardinis
Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been made to stop the AIDS pandemic. A major success of medical research has been the development of the highly active antiretroviral therapy and its availability to an increasing number of people worldwide, with a considerable effect on survival. However, a safe and effective vaccine able to prevent and eradicate the HIV pandemic is still lacking...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669838/effects-of-adjuvants-on-hiv-1-envelope-glycoprotein-sosip-trimers-in-vitro
#4
Gabriel Ozorowski, Albert Cupo, Michael Golabek, Michelle LoPiccolo, Thomas A Ketas, Matt Cavallary, Christopher A Cottrell, P J Klasse, Andrew B Ward, John P Moore
Native-like, soluble, recombinant SOSIP trimers of various designs and based on several env genes of human immunodeficiency virus type 1 (HIV-1) are being tested as immunogens in different animal models. These experiments almost always involve co-formulating the trimers with an adjuvant to boost the magnitude of the immune responses. One factor relevant to the choice of an adjuvant is that it should not physically damage the immunogen or impede its ability to present relevant epitopes. As examples, an adjuvant formulation that includes harsh detergents could disrupt the structural integrity of a trimer, and any charged compounds in the formulation could bind to counter-charged regions of the trimer and physically occlude nearby epitopes...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669274/superinfection-drives-hiv-neutralizing-antibody-responses-from-several-b-cell-lineages-that-contribute-to-a-polyclonal-repertoire
#5
Katherine L Williams, Bingjie Wang, Dana Arenz, James A Williams, Adam S Dingens, Valerie Cortez, Cassandra A Simonich, Stephanie Rainwater, Dara A Lehman, Kelly K Lee, Julie Overbaugh
Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses develop. However, far less is known about responses developed by superinfected individuals who acquire two distinct HIV strains. Here, we isolated HIV-specific mAbs from a superinfected individual with a broad plasma response...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29667004/the-development-of-hiv-vaccines-targeting-gp41-membrane-proximal-external-region-mper-challenges-and-prospects
#6
REVIEW
Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang
A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs)...
April 17, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29666292/human-immunodeficiency-virus-tat-protein-aids-v-region-somatic-hypermutation-in-human-b-cells
#7
Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D Scharff
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29666227/anti-hiv-1-b-cell-responses-are-dependent-on-b-cell-precursor-frequency-and-antigen-binding-affinity
#8
Pia Dosenovic, Ervin E Kara, Anna-Klara Pettersson, Andrew T McGuire, Matthew Gray, Harald Hartweger, Eddy S Thientosapol, Leonidas Stamatatos, Michel C Nussenzweig
The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29662494/evolution-of-neutralization-response-in-hiv-1-subtype-c-infected-individuals-exhibiting-broad-cross-clade-neutralization-of-hiv-1-strains
#9
Narayanaiah Cheedarla, Babu Hemalatha, Brahmaiah Anangi, Kannan Muthuramalingam, Murugesan Selvachithiram, Pattabiraman Sathyamurthi, Nandagopal Kailasam, Raghavan Varadarajan, Soumya Swaminathan, Srikanth Prasad Tripathy, S Kalyanaraman Vaniambadi, D Ramanathan Vadakkupattu, Luke Elizabeth Hanna
Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10-30% of infected individuals produce broadly neutralizing antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29662199/a-single-injection-of-crystallizable-fragment-domain-modified-antibodies-elicits-durable-protection-from-shiv-infection
#10
Rajeev Gautam, Yoshiaki Nishimura, Natalie Gaughan, Anna Gazumyan, Till Schoofs, Alicia Buckler-White, Michael S Seaman, Bruce J Swihart, Dean A Follmann, Michel C Nussenzweig, Malcolm A Martin
In the absence of an effective and safe vaccine against HIV-1, the administration of broadly neutralizing antibodies (bNAbs) represents a logical alternative approach to prevent virus transmission. Here, we introduced two mutations encoding amino acid substitutions (M428L and N434S, collectively referred to as 'LS') into the genes encoding the crystallizable fragment domains of the highly potent HIV-specific 3BNC117 and 10-1074 bNAbs to increase their half-lives and evaluated their efficacy in blocking infection following repeated low-dose mucosal challenges of rhesus macaques (Macaca mulatta) with the tier 2 SHIVAD8-EO ...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29662026/the-hard-way-towards-an-antibody-based-hiv-1-env-vaccine-lessons-from-other-viruses
#11
REVIEW
Oliver Ringel, Vincent Vieillard, Patrice Debré, Jutta Eichler, Hildegard Büning, Ursula Dietrich
Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of "classical" vaccine approaches, which are mostly due to the biological properties of the virus itself...
April 15, 2018: Viruses
https://www.readbyqxmd.com/read/29651286/iga-targeting-human-immunodeficiency-virus-1-envelope-gp41-triggers-antibody-dependent-cellular-cytotoxicity-cross-clade-and-cooperates-with-gp41-specific-igg-to-increase-cell-lysis
#12
Maxence Duchemin, Marwa Khamassi, Lin Xu, Daniela Tudor, Morgane Bomsel
The protective efficacy of human immunodeficiency virus-1 (HIV-1) antibodies (Abs) remains mostly correlated with their in vitro neutralizing activity engaging their Fab region. However, anti-HIV-1 Abs also mediate a broad array of Fc-mediated effector functions including Ab-dependent cellular cytotoxicity (ADCC), which depend primarily on the Ab isotype. While ADCC is commonly associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29648914/tx99-is-a-neutralizing-monoclonal-antibody-against-mouse-tigit
#13
Yuho Nakamura, Keisuke Naito, Yumi Yamashita-Kanemaru, Daisuke Komori, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
T cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory immunoreceptor expressed on NK cells, effector and memory T cells, and regulatory T cells (Tregs). The ligands for TIGIT are CD155 (PVR) and CD112 (PVRL2, nectin-2), which are broadly expressed on hematopoietic cells and nonhematopoietic cells. TIGIT negatively regulates antitumor responses, but promotes autoimmune reaction. Although neutralizing anti-human TIGIT mAbs are under clinical trials for cancers, how the blockade of TIGIT interaction with the ligands shows tumor immunity still remains unclear...
April 12, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29643370/how-single-mutations-affect-viral-escape-from-broad-and-narrow-antibodies-to-h1-influenza-hemagglutinin
#14
Michael B Doud, Juhye M Lee, Jesse D Bloom
Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin's receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects...
April 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29643249/neutralizing-antibody-responses-following-long-term-vaccination-with-hiv-1-env-gp140-in-guinea-pigs
#15
Christine A Bricault, James M Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L Shields, Bronwyn M Gunn, George H Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P Nkolola, Galit Alter, Bing Chen, Kathryn E Stephenson, Nicole Doria-Rose, John R Mascola, Michael S Seaman, Dan H Barouch
A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we report the immunogenicity of longitudinal prime/boost vaccination regimens over a period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140 protein immunogens. We assessed vaccine regimens that included a monovalent clade C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140 (ABCM)...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29628926/novel-platforms-for-the-development-of-a-universal-influenza-vaccine
#16
REVIEW
Arun Kumar, Trine Sundebo Meldgaard, Sylvie Bertholet
Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29624884/the-molecular-mechanism-of-two-coreceptor-binding-site-antibodies-x5-and-17b-neutralizing-hiv-1-insights-from-molecular-dynamics-simulation
#17
Yan Zhang, Jingjing Guo, Le Huang, Jiaqi Tian, Xiaojun Yao, Huanxiang Liu
The coreceptor binding site of gp120 plays an important role in HIV entry into host cell. X5 and 17b are typical coreceptor binding site antibodies with the ability to broadly neutralize HIV. Thus, here, to study the neutralizing mechanism of two antibodies and identify the source of two antibodies with different neutralizing ability, we performed molecular dynamics simulations for the complexes of X5 and 17b with gp120 and CD4. The simulation results indicate X5 and 17b mainly affects CD4 and coreceptor binding sites...
April 6, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29618644/molecular-basis-of-unusually-high-neutralization-resistance-in-tier-3-hiv-1-strain-253-11
#18
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E Pavillet, Samuel Mundia Kariuki, Emily N Tangie, Jean-Philippe Julien, Jeffrey R Dorfman
Understanding the mechanisms used by HIV-1 to evade antibody neutralization may contribute to the design of a high-coverage vaccine. The tier 3 virus 253-11, is poorly neutralized by subtype-matched and subtype C sera, even when compared to other tier 3 viruses, and is also recognized poorly by V3/glycan targeting monoclonal antibodies. We found that sequence polymorphism in the V3 loop and N-linked glycosylation sites only minimally contribute to the high neutralization resistance of 253-11. Interestingly, the 253-11 membrane proximal external region (MPER) is rarely recognized by sera in the context of the wild-type virus, but is commonly recognized in the context of an HIV-2 chimeric virus, suggesting steric or kinetic hindrance of binding to MPER in the native Env...
April 4, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29617879/prevalence-and-significance-of-substitutions-in-the-fusion-protein-of-respiratory-syncytial-virus-resulting-in-neutralization-escape-from-antibody-medi8897
#19
Qing Zhu, Bin Lu, Patrick McTamney, Susan Palaszynski, Seme Diallo, Kuishu Ren, Nancy D Ulbrandt, Nicole Kallewaard, Weijia Wang, Fiona Fernandes, Steve Wong, Catherine Svabek, Brian Moldt, Mark T Esser, Hong Jing, JoAnn A Suzich
Background: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children. To date, no vaccine is approved for the broad population of healthy infants. MEDI8897, a potent anti-RSV fusion antibody with extended serum half-life is currently under clinical investigation as a potential passive RSV vaccine for all infants. As an RNA virus, RSV is prone to mutation, the possibility of viral escape from MEDI8897 neutralization is a potential concern...
March 30, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29610325/a-small-molecule-fragment-that-emulates-binding-of-receptor-and-broadly-neutralizing-antibodies-to-influenza-a-hemagglutinin
#20
Rameshwar U Kadam, Ian A Wilson
The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N -cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
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