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HIV neutralizing antibody

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
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
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
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
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
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
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
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
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
Yuyang Tang, Alvin M George, Oksana Petrechko, Franklin J Nouvet, Stephanie D Sweet, Yuetsu Tanaka, Brian S Imbiakha, Guochun Jiang, Wei Gao, Kathryn Anastos, James E K Hildreth
Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV-1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1...
April 25, 2018: MSphere
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
Luis R Castillo-Menendez, Kristen Witt, Nicole Espy, Amy Princiotto, Navid Madani, Beatriz Pacheco, Andrés Finzi, Joseph Sodroski
The mature envelope glycoprotein (Env) spike on the surface of human immunodeficiency virus (HIV-1) infected cells and virions is derived by proteolytic cleavage of a trimeric gp160 glycoprotein precursor. In these studies, we compared the conformations of cleaved and uncleaved membrane Envs with truncated cytoplasmic tails to those of stabilized soluble gp140 SOSIP.664 Env trimers. Deletion of the gp41 cytoplasmic tail did not significantly affect the sensitivity of viruses with the HIV-1AD8 Env to inhibition by antibodies or a CD4-mimetic compound...
April 4, 2018: Journal of Virology
Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li
Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (TFH ) cells, and T follicular regulatory (TFR ) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses...
April 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Soraya Sangjan, Silawun Ampol, Guo Jia-Jun, Sutchana Tabprasit, Navin Horthongkham, Thippawan Chuenchitra, Pattama Ekpo, Wannee Kantakamalakul
BACKGROUND: There have been a few studies aimed at identifying epitopes of ADCC-inducing antibodies when compared to those of neutralizing antibodies and cytotoxic T lymphocytes against a variety of HIV-1 clades. OBJECTIVE: To map the common ADCC epitopes of HIV-1 CRF01_AE. METHODS: We screened 65 sera of confirmed early HIV-1 CRF01_AE infected individuals for ADCC antibody against gp120 utilizing an EGFP-CEM-NKr flow cytometric assay. Sera with high ADCC antibody were then examined against ADCC epitopes using the complete HIV-1 CRF01_AE gp160- and subtype A Gag-overlapping peptide sets which were divided into 7 pools:E1-E7 and 5 pools:G1-G5, respectively...
March 31, 2018: Asian Pacific Journal of Allergy and Immunology
Max Crispin, Andrew B Ward, Ian A Wilson
Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response...
March 29, 2018: Annual Review of Biophysics
Christopher O Barnes, Harry B Gristick, Natalia T Freund, Amelia Escolano, Artem Y Lyubimov, Harald Hartweger, Anthony P West, Aina E Cohen, Michel C Nussenzweig, Pamela J Bjorkman
Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy requires understanding how antibodies interact with the native oligomannose and complex-type N-glycan shield that hides most protein epitopes on HIV-1 envelope (Env). Here we present crystal structures, including a 3.8-Å X-ray free electron laser dataset, of natively glycosylated Env trimers complexed with BG18, the most potent V3/N332gp120 glycan-targeting bNAb reported to date...
March 28, 2018: Nature Communications
Ina Fetzer, Matthew R Gardner, Meredith E Davis-Gardner, Neha R Prasad, Barnett Alfant, Jesse A Weber, Michael Farzan
The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1...
March 28, 2018: Journal of Virology
Deogratius Ssemwanga, Nicole A Doria-Rose, Andrew D Redd, Andrea R Shiakolas, Andrew F Longosz, Rebecca N Nsubuga, Billy N Mayanja, Gershim Asiki, Janet Seeley, Anatoli Kamali, Amy Ransier, Samuel Darko, Michael P Walker, Daniel Bruno, Craig Martens, Daniel Douek, Stephen F Porcella, Thomas C Quinn, John R Mascola, Pontiano Kaleebu
This report describes the identification of a genetically confirmed linked heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a woman with chronic HIV infection who acquired a second strain of the virus from her husband. Serum neutralizing antibody (NAb) responses against their homologous and heterologous viruses, including the superinfecting strain, in the woman and her husband were examined before and after onset of HIV-SI. The woman displayed a moderately potent and broad anti-HIV NAb response prior to superinfection but did not possess NAb activity against the superinfecting strain...
March 22, 2018: Journal of Infectious Diseases
Muzafar Jan, Chitra Upadhyay, José Alcami Pertejo, Catarina E Hioe, Sunil K Arora
Lectins that target N-glycans on the surface of HIV-1 envelope (Env) glycoprotein have the potential for use as antiviral agents. Although progress has been made in deciphering the molecular details of lectin and Env glycan interaction, further studies are needed to better understand Env glycan heterogeneity among HIV-1 isolates and its influence on virus-neutralization sensitivity to lectins. This study evaluated a panel of lectins with fine specificity for distinct oligosaccharides and assessed their ability to inhibit infection of HIV-1 viruses known to have differing sensitivity to anti-HIV Env antibodies...
2018: PloS One
Vidya S Shivatare, Sachin S Shivatare, Chang-Chun David Lee, Chi-Hui Liang, Kuo-Shiang Liao, Yang-Yu Cheng, Gannerla Saidachary, Chung-Yi Wu, Nan-Horng Lin, Peter D Kwong, Dennis R Burton, Chung-Yi Wu, Chi-Huey Wong
The development of HIV vaccine has been hampered by the extraordinary mutability and genetic diversity of the virus, particularly the substantial sequence diversity of gp120 and gp 41 envelope glycoproteins existing in more than 2,000 HIV variants. The highly diverse glycans on HIV spikes are commonly considered as immunologically silent self-antigens; however, the discovery of highly potent broadly neutralizing antibodies (bNAbs) from HIV patients targeting the viral surface glycans has raised a major question about the origin of their antigens...
March 26, 2018: Journal of the American Chemical Society
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