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https://www.readbyqxmd.com/read/28387330/profiling-the-neutralizing-antibody-response-in-chronically-hiv-1-crf07_bc-infected-intravenous-drug-users-na%C3%A3-ve-to-antiretroviral-therapy
#1
Xintao Hu, Yuanyuan Hu, Chunhong Zhao, Hongmei Gao, Kelli M Greene, Li Ren, Liying Ma, Yuhua Ruan, Marcella Sarzotti-Kelsoe, David C Montefiori, Kunxue Hong, Yiming Shao
Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B'-infected individuals in China...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381572/improving-the-expression-and-purification-of-soluble-recombinant-native-like-hiv-1-envelope-glycoprotein-trimers-by-targeted-sequence-changes
#2
Rajesh P Ringe, Gabriel Ozorowski, Anila Yasmeen, Albert Cupo, Victor M Cruz Portillo, Pavel Pugach, Michael Golabek, Kimmo Rantalainen, Lauren G Holden, Christopher A Cottrell, Ian A Wilson, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore
Soluble, recombinant native-like envelope glycoprotein (Env) trimers of various human immunodeficiency virus type 1 (HIV-1) genotypes are being developed for structural studies and as vaccine candidates aimed at the induction of broadly neutralizing antibodies (bNAbs). The prototypic design is designated SOSIP.664, but many HIV-1 env genes do not yield fully native-like trimers efficiently. One such env gene is CZA97.012 from a neutralization-resistant (Tier-2) clade C virus. As appropriately purified, native-like CZA97...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28360890/driving-hiv-1-into-a-vulnerable-corner-by-taking-advantage-of-viral-adaptation-and-evolution
#3
REVIEW
Shigeyoshi Harada, Kazuhisa Yoshimura
Anti-retroviral therapy (ART) is crucial for controlling human immunodeficiency virus type-1 (HIV-1) infection. Recently, progress in identifying and characterizing highly potent broadly neutralizing antibodies has provided valuable templates for HIV-1 therapy and vaccine design. Nevertheless, HIV-1, like many RNA viruses, exhibits genetically diverse populations known as quasispecies. Evolution of quasispecies can occur rapidly in response to selective pressures, such as that exerted by ART and the immune system...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28315414/the-dynamics-of-hcv-specific-antibody-responses-in-hiv-hcv-patients-on-long-term-antiretroviral-therapy
#4
Silvia Lee, Alfred Laiman, Martyn A French, James Flexman, Mark W Watson, Patricia Price
Antibody responses have not been fully characterised in chronically HIV/HCV patients receiving antiretroviral therapy (ART). Seventeen HIV/HCV patients receiving ART were followed for a median (range) interval of 597 (186-766) weeks. Prior to ART, HIV/HCV patients had lower levels of antibodies reactive with HCV core and JFH-1, and lower genotype cross-reactive neutralising antibodies (nAb) titres, than HCV patients. Levels of JFH-1 reactive antibody increased on ART, irrespective of CD4(+) T-cell counts or changes in serum ALT levels...
March 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28301274/neutralizing-antibodies-against-adenovirus-type-2-in-normal-and-hiv-1-infected-subjects-implications-for-use-of-ad2-vectors-in-vaccines
#5
Qianqian Li, Qiang Liu, Weijing Huang, Aijing Song, Chenyan Zhao, Jiajing Wu, Youchun Wang
Pre-existing neutralizing antibodies (NAbs) directed against vaccine vectors have attracted considerable research attention. Therefore, our aim was to establish a high-throughput economical neutralization assay to investigate the epidemiology of adenovirus type 2 (Ad2)-specific immunity in China and developed countries, including in a Chinese Human immunodeficiency virus (HIV)-1-infected population, and to guide the application of Ad2-vectored vaccines. We established a FluoroSpot-based anti-Ad2-virus neutralization assay using a recombinant replication-deficient Ad2 that expresses enhanced green fluorescent protein and standardized the critical parameters, including the choice of cell line, cell concentration, viral infective dose, and incubation time...
March 16, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28279830/effects-of-partially-dismantling-the-cd4-binding-site-glycan-fence-of-hiv-1-envelope-glycoprotein-trimers-on-neutralizing-antibody-induction
#6
Ema T Crooks, Keiko Osawa, Tommy Tong, Samantha L Grimley, Yang D Dai, Robert G Whalen, Daniel W Kulp, Sergey Menis, William R Schief, James M Binley
Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits (PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to improve nAb responses by removing the N362 glycan that also lines the CD4bs. All 4 rabbits developed nAbs. One targeted the N197 glycan hole like our previous sera. Two sera depended on the N463 glycan, again suggesting CD4bs overlap...
May 2017: Virology
https://www.readbyqxmd.com/read/28237764/evaluation-of-a-novel-multi-immunogen-vaccine-strategy-for-targeting-4e10-10e8-neutralizing-epitopes-on-hiv-1-gp41-membrane-proximal-external-region
#7
Saikat Banerjee, Heliang Shi, Marisa Banasik, Hojin Moon, William Lees, Yali Qin, Andrew Harley, Adrian Shepherd, Michael W Cho
The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone...
May 2017: Virology
https://www.readbyqxmd.com/read/28089302/germinal-center-lymphocyte-ratios-and-successful-hiv-vaccines
#8
Paula Gonzalez-Figueroa, Jonathan A Roco, Carola G Vinuesa
Current HIV vaccines are poor inducers of neutralizing antibodies (nAbs). A recent study in Cell Reports used serial fine-needle aspirates from rhesus macaque lymph nodes following HIV-1 surface envelope glycoprotein (Env) trimer immunization, generating a substantial production of HIV-1 nAbs. A remarkable correlation was found between antibody titers and a high frequency and ratio of germinal center B and T follicular helper (TFH) lymphocytes.
January 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28046039/humoral-immunity-to-primary-smallpox-vaccination-impact-of-childhood-versus-adult-immunization-on-vaccinia-vector-vaccine-development-in-military-populations
#9
Bonnie M Slike, Matthew Creegan, Mary Marovich, Viseth Ngauy
Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i...
2017: PloS One
https://www.readbyqxmd.com/read/27941965/cd4-cd8-ratio-and-kt-ratio-predict-yellow-fever-vaccine-immunogenicity-in-hiv-infected-patients
#10
Vivian I Avelino-Silva, Karina T Miyaji, Peter W Hunt, Yong Huang, Marisol Simoes, Sheila B Lima, Marcos S Freire, Helio H Caiaffa-Filho, Marisa A Hong, Dayane Alves Costa, Juliana Zanatta C Dias, Natalia B Cerqueira, Anna Shoko Nishiya, Ester Cerdeira Sabino, Ana M Sartori, Esper G Kallas
BACKGROUND: HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. METHODS: We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27880897/direct-probing-of-germinal-center-responses-reveals-immunological-features-and-bottlenecks-for-neutralizing-antibody-responses-to-hiv-env-trimer
#11
Colin Havenar-Daughton, Diane G Carnathan, Alba Torrents de la Peña, Matthias Pauthner, Bryan Briney, Samantha M Reiss, Jennifer S Wood, Kirti Kaushik, Marit J van Gils, Sandy L Rosales, Patricia van der Woude, Michela Locci, Khoa M Le, Steven W de Taeye, Devin Sok, Ata Ur Rasheed Mohammed, Jessica Huang, Sanjeev Gumber, AnaPatricia Garcia, Sudhir P Kasturi, Bali Pulendran, John P Moore, Rafi Ahmed, Grégory Seumois, Dennis R Burton, Rogier W Sanders, Guido Silvestri, Shane Crotty
Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27853456/patterns-of-hiv-siv-prevention-and-control-by-passive-antibody-immunization
#12
REVIEW
Hiroyuki Yamamoto, Tetsuro Matano
Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27853288/enhancing-virion-tethering-by-bst2-sensitizes-productively-and-latently-hiv-infected-t-cells-to-adcc-mediated-by-broadly-neutralizing-antibodies
#13
Tram N Q Pham, Sabelo Lukhele, Frédéric Dallaire, Gabrielle Perron, Éric A Cohen
Binding of anti-HIV antibodies (Abs) to envelope (Env) glycoproteins on infected cells can mark them for elimination via antibody-dependent cell-mediated cytotoxicity (ADCC). BST2, a type I interferon (IFN)-stimulated restriction factor that anchors nascent Env-containing virions at the surface of infected cells has been shown to enhance ADCC functions. In a comprehensive analysis of ADCC potency by neutralizing anti-HIV Abs (NAbs), we show in this study that NAbs are capable of mediating ADCC against HIV-infected T cells with 3BNC117, PGT126 and PG9 being most efficient...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27820858/saturation-mutagenesis-of-the-hiv-1-envelope-cd4-binding-loop-reveals-residues-controlling-distinct-trimer-conformations
#14
Maria Duenas-Decamp, Li Jiang, Daniel Bolon, Paul R Clapham
The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27643887/neutralization-resistant-hiv-1-primary-isolates-from-antiretroviral-na%C3%A3-ve-chronically-infected-children-in-india
#15
Muzamil Ashraf Makhdoomi, Deepti Singh, Ambili Nair Pananghat, Rakesh Lodha, Sushil Kumar Kabra, Kalpana Luthra
Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been extensively tested against pesudoviruses of diverse strains. We generated and characterized HIV-1 primary isolates from antiretroviral naïve infected Indian children, and determined their susceptibility to known NAbs. All the 8 isolates belonged to subtype-C and were R5 tropic. Majority of these viruses were resistant to neutralization by NAbs, suggesting that the bnAbs, known to efficiently neutralize pseudoviruses (adult and pediatric) of different strains, are less effective against pediatric primary isolates...
December 2016: Virology
https://www.readbyqxmd.com/read/27627672/sequential-and-simultaneous-immunization-of-rabbits-with-hiv-1-envelope-glycoprotein-sosip-664-trimers-from-clades-a-b-and-c
#16
P J Klasse, Celia C LaBranche, Thomas J Ketas, Gabriel Ozorowski, Albert Cupo, Pavel Pugach, Rajesh P Ringe, Michael Golabek, Marit J van Gils, Miklos Guttman, Kelly K Lee, Ian A Wilson, Salvatore T Butera, Andrew B Ward, David C Montefiori, Rogier W Sanders, John P Moore
We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were delivered either simultaneously (as a mixture of clade A + B trimers) or sequentially over a 73-week period. Autologous, Tier-2 neutralizing antibody (NAb) responses were generated to the clade A and clade B trimers in the bivalent mixture...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27545891/holes-in-the-glycan-shield-of-the-native-hiv-envelope-are-a-target-of-trimer-elicited-neutralizing-antibodies
#17
Laura E McCoy, Marit J van Gils, Gabriel Ozorowski, Terrence Messmer, Bryan Briney, James E Voss, Daniel W Kulp, Matthew S Macauley, Devin Sok, Matthias Pauthner, Sergey Menis, Christopher A Cottrell, Jonathan L Torres, Jessica Hsueh, William R Schief, Ian A Wilson, Andrew B Ward, Rogier W Sanders, Dennis R Burton
A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position...
August 30, 2016: Cell Reports
https://www.readbyqxmd.com/read/27440894/induction-of-heterologous-tier-2-hiv-1-neutralizing-and-cross-reactive-v1-v2-specific-antibodies-in-rabbits-by-prime-boost-immunization
#18
Samantha Townsley, Zeinab Mohamed, Wenjin Guo, Jennifer McKenna, Brad Cleveland, Celia LaBranche, David Beaumont, Xiaoying Shen, Nicole L Yates, Abraham Pinter, Georgia D Tomaras, Guido Ferrari, David C Montefiori, Shiu-Lok Hu
UNLABELLED: Poxvirus prime-protein boost used in the RV144 trial remains the only immunization strategy shown to elicit a modest level of protection against HIV-1 acquisition in humans. Although neutralizing antibodies (NAb) were generated, they were against sensitive viruses, not the more resistant "tier 2" isolates that dominate circulating strains. Instead, risk reduction correlated with antibodies recognizing epitopes in the V1/V2 region of HIV-1 envelope glycoprotein (Env). Here, we examined whether tier 2 virus NAb and V1/V2-specific non-NAb could be elicited by a poxvirus prime-gp120 boost strategy in a rabbit model...
October 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27388013/hiv-1-escapes-from-n332-directed-antibody-neutralization-in-an-elite-neutralizer-by-envelope-glycoprotein-elongation-and-introduction-of-unusual-disulfide-bonds
#19
Tom L G M van den Kerkhof, Steven W de Taeye, Brigitte D Boeser-Nunnink, Dennis R Burton, Neeltje A Kootstra, Hanneke Schuitemaker, Rogier W Sanders, Marit J van Gils
BACKGROUND: Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design. RESULTS: Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection...
July 7, 2016: Retrovirology
https://www.readbyqxmd.com/read/27368421/increased-hiv-1-sensitivity-to-neutralizing-antibodies-by-mutations-in-the-env-v3-coding-region-for-resistance-to-cxcr4-antagonists
#20
Yuta Hikichi, Masaru Yokoyama, Taichiro Takemura, Masayuki Fujino, Sei Kumakura, Yosuke Maeda, Naoki Yamamoto, Hironori Sato, Tetsuro Matano, Tsutomu Murakami
HIV-1 passage in cell culture in the presence of chemokine receptor antagonists can result in selection of viruses with env mutations that confer resistance to these inhibitors. In the present study, we examined the effect of HIV-1env mutations that confer resistance to CXCR4 antagonists on envelope (Env) sensitivity to neutralizing antibodies (NAbs). Serial passage of CXCR4-tropic HIV-1 NL4-3 in PM1/CCR5 cells under CXCR4 antagonists KRH-3955, AMD3100 and AMD070 yielded two KRH-3955-resistant, one AMD3100-resistant and one AMD070-resistant viruses...
September 2016: Journal of General Virology
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