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https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#1
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28841647/probing-the-compartmentalization-of-hiv-1-in-the-central-nervous-system-through-its-neutralization-properties
#2
Karl Stefic, Antoine Chaillon, Mélanie Bouvin-Pley, Alain Moreau, Martine Braibant, Frédéric Bastides, Guillaume Gras, Louis Bernard, Francis Barin
Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28835491/hiv-1-cross-reactive-primary-virus-neutralizing-antibody-response-elicited-by-immunization-in-non-human-primate
#3
Yimeng Wang, Sijy O'Dell, Hannah L Turner, Chi-I Chiang, Lin Lei, Javier Guenaga, Richard Wilson, Paola Martinez-Murillo, Nicole Doria-Rose, Andrew B Ward, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam, Yuxing Li
Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates predominantly elicit tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28834745/improving-the-immunogenicity-of-native-like-hiv-1-envelope-trimers-by-hyperstabilization
#4
Alba Torrents de la Peña, Jean-Philippe Julien, Steven W de Taeye, Fernando Garces, Miklos Guttman, Gabriel Ozorowski, Laura K Pritchard, Anna-Janina Behrens, Eden P Go, Judith A Burger, Edith E Schermer, Kwinten Sliepen, Thomas J Ketas, Pavel Pugach, Anila Yasmeen, Christopher A Cottrell, Jonathan L Torres, Charlotte D Vavourakis, Marit J van Gils, Celia LaBranche, David C Montefiori, Heather Desaire, Max Crispin, Per Johan Klasse, Kelly K Lee, John P Moore, Andrew B Ward, Ian A Wilson, Rogier W Sanders
The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28792942/hiv-1-neutralizing-antibody-induced-by-simian-adenovirus-and-poxvirus-mva-vectored-bg505-native-like-envelope-trimers
#5
Silvia Capucci, Edmund G Wee, Torben Schiffner, Celia C LaBranche, Nicola Borthwick, Albert Cupo, Jonathan Dodd, Hansi Dean, Quentin Sattentau, David Montefiori, Per J Klasse, Rogier W Sanders, John P Moore, Tomáš Hanke
Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1...
2017: PloS One
https://www.readbyqxmd.com/read/28696188/evolution-of-cross-neutralizing-antibodies-and-mapping-epitope-specificity-in-plasma-of-chronic-hiv-1-infected-antiretroviral-therapy-na%C3%A3-ve-children-from-india
#6
Muzamil A Makhdoomi, Lubina Khan, Sanjeev Kumar, Heena Aggarwal, Ravinder Singh, Rakesh Lodha, Mohit Singla, Bimal K Das, Sushil K Kabra, Kalpana Luthra
Delineating the factors leading to the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope specificities generates useful information for vaccine design. This is the first longitudinal study to assess the plasma-neutralizing antibody response and neutralizing determinants in HIV-1-infected children from India. We enrolled 26 and followed up 20 antiretroviral therapy (ART)-naïve, asymptomatic, chronic HIV-1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma samples neutralized ≥50 % of subtypes A, B and C tier 2 viruses at an ID50 titre ≥150...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#7
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28615205/intrasubtype-b-hiv-1-superinfection-correlates-with-delayed-neutralizing-antibody-response
#8
Gabriel A Wagner, Elise Landais, Gemma Caballero, Pham Phung, Sergei L Kosakovsky Pond, Pascal Poignard, Douglas D Richman, Susan J Little, Davey M Smith
Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection...
September 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28599793/a-cross-reacting-material-crm197-conjugate-vaccine-induces-diphtheria-toxin-neutralizing-antibody-response-in-children-and-adolescents-infected-or-not-with-hiv
#9
Giselle P Silva, Rafaela S Santos, Wânia F Pereira-Manfro, Bianca Ferreira, Daniella M Barreto, Ana Cristina C Frota, Cristina B Hofer, Lucimar G Milagres
Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM197) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0...
June 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#10
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs) but can also expose binding sites for some types of nonneutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
August 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539448/virological-control-by-the-cd4-binding-site-antibody-n6-in-simian-human-immunodeficiency-virus-infected-rhesus-monkeys
#11
Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D Schmidt, Jinghe Huang, Richard A Koup, Michael S Seaman, Brandon F Keele, John R Mascola, Mark Connors, Dan H Barouch
Passive immunotherapy against HIV-1 will most likely require broadly neutralizing antibodies (bnAbs) with maximum breadth and potency to ensure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross-clade pseudoviruses. We evaluated the in vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically simian-human immunodeficiency virus (SHIV)-SF162P3-infected macaques...
August 15, 2017: Journal of Virology
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
#12
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
#13
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...
June 15, 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
#14
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
#15
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...
June 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
#16
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...
June 3, 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
#17
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
#18
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
#19
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.
February 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
#20
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
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