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Vaccination in HIV

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https://www.readbyqxmd.com/read/29775847/strategies-for-a-multi-stage-neutralizing-antibody-based-hiv-vaccine
#1
REVIEW
Raiees Andrabi, Jinal N Bhiman, Dennis R Burton
A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approaches for immunogen design, the development of novel animal models for immunogen evaluation and advanced technologies to interrogate antibody responses...
May 15, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29773829/sequential-immunizations-with-a-panel-of-hiv-1-env-virus-like-particles-coach-immune-system-to-make-broadly-neutralizing-antibodies
#2
Teena Mohan, Zachary Berman, Sang-Moo Kang, Bao-Zhong Wang
Broadly neutralizing antibodies (bnAbs) are correlated with passive HIV/SHIV protection and are desirable components of a HIV protective immunity. In the current study, we have designed a sequential-immunization strategy with a panel of envelope glycoprotein (Env)-enriched virus-like particles (VLPs) from various HIV-1 clades (A-E) to elicit bnAbs with high breadth and potency of neutralization in rabbits. We have compared this regimen with repetitive immunizations of individual Env (subtype B) VLPs or a mixture of various Env VLPs...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772941/recent-advances-in-the-discovery-and-development-of-tlr-ligands-as-novel-therapeutics-for-chronic-hbv-and-hiv-infections
#3
Keye Du, Jia Liu, Ruth Broering, Xiaoyong Zhang, Dongliang Yang, Ulf Dittmer, Mengji Lu
Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands ...
May 17, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29772781/the-potential-role-of-fc-receptor-functions-in-the-development-of-a-universal-influenza-vaccine
#4
Sinthujan Jegaskanda
Despite global vaccination efforts, influenza virus continues to cause yearly epidemics and periodic pandemics throughout most of the world. Many of us consider the generation of broader, potent and long-lasting immunity against influenza viruses as critical in curtailing the global health and economic impact that influenza currently plays. To date, classical vaccinology has relied on the generation of neutralizing antibodies as the benchmark to measure vaccine effectiveness. However, recent developments in numerous related fields of biomedical research including, HIV, HSV and DENV have emphasized the importance of Fc-mediate effector functions in pathogenesis and immunity...
May 17, 2018: Vaccines
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#5
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29769533/structure-of-a-cleavage-independent-hiv-env-recapitulates-the-glycoprotein-architecture-of-the-native-cleaved-trimer
#6
Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C Diwanji, Robyn L Stanfield, Andrew B Ward, Max Crispin, Richard T Wyatt, Ian A Wilson
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769530/comparison-of-the-genotypic-and-phenotypic-properties-of-hiv-1-standard-subtype-b-and-subtype-b-b-env-molecular-clones-derived-from-infections-in-china
#7
Hui Xie, Jianhui Nie, Qingqing Chen, Weijin Huang, Youchun Wang
Although a number of standardized human immunodeficiency virus 1 (HIV-1) pseudoviruses have been generated to assess neutralizing antibodies, subtype B/B' has not been comprehensively characterized either genotypically or phenotypically. Full-length env genes were isolated from plasma samples derived from B/B'-infected individuals, including former plasma donors and men who had sex with men. The neutralization properties of these pseudoviruses were determined by testing against sCD4, 16 neutralizing monoclonal antibodies and 44 plasma samples, including samples from those infected with the three major prevalent clades in China...
May 16, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29769351/protein-phosphatase-1%C3%AE-interacts-with-venezuelan-equine-encephalitis-virus-capsid-protein-and-regulates-viral-replication-through-modulation-of-capsid-phosphorylation
#8
Brian D Carey, Tatiana Ammosova, Chelsea Pinkham, Xionghao Lin, Weidong Zhou, Lance A Liotta, Sergei Nekhai, Kylene Kehn-Hall
Protein Phosphatase 1 (PP1) is a serine/threonine phosphatase which has been implicated in the regulation of a number of viruses including HIV-1, Ebolavirus and Rift Valley fever virus. Catalytic subunits of PP1 (PP1α, PP1β, or PP1γ) interact with a host of regulatory subunits and target a wide variety of cellular substrates through a combination of short binding motifs, including an RVxF motif present in the majority of PP1 regulatory subunits. Targeting the RVxF interacting site on PP1 with the small molecule, 1E7-03 inhibits HIV-1, Ebolavirus, and Rift Valley fever virus replication...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769062/seroprevalence-of-hiv-htlv-cmv-hbv-and-rubella-virus-infections-in-pregnant-adolescents-who-received-care-in-the-city-of-bel%C3%A3-m-par%C3%A3-northern-brazil
#9
Aubaneide Batista Guerra, Leonardo Quintão Siravenha, Rogério Valois Laurentino, Rosimar Neris Martins Feitosa, Vânia Nakauth Azevedo, Antonio Carlos Rosário Vallinoto, Ricardo Ishak, Luiz Fernando Almeida Machado
BACKGROUND: Prenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil. METHODS: A cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010...
May 16, 2018: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/29768174/hiv-1-vaccines-based-on-antibody-identification-b-cell-ontogeny-and-epitope-structure
#10
REVIEW
Peter D Kwong, John R Mascola
HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural characteristics of these antibodies and the epitopes they recognize is enabling new approaches to vaccine design...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29762162/genetic-characterization-of-the-hiv-1-reservoir-after-vacc-4x-and-romidepsin-therapy-in-hiv-1-infected-individuals
#11
Anni Winckelmann, Vincent Morcilla, Wei Shao, Mariane H Schleimann, Jesper F Højen, Timothy E Schlub, Paul W Denton, Lars Østergaard, Ole S Søgaard, Martin Tolstrup, Sarah Palmer
OBJECTIVE: Therapeutic HIV-1 immunization followed by latency reversal has been suggested as a strategy to eradicate HIV-1. Here we investigate the phylogenetic composition of the HIV-1 regions targeted by the therapeutic HIV-1 peptide vaccine Vacc-4x in participants in a clinical trial. DESIGN: Seventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of Vacc-4x followed by three doses of romidepsin. Seven study participants were selected for sequencing analysis...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29762161/anti-hiv-igm-protects-against-mucosal-shiv-transmission
#12
Siqi Gong, Khamis Tomusange, Viraj Kulkarni, Opeyemi S Adeniji, Samir K Lakhashe, Dinesh Hariraju, Amanda Strickland, Elizabeth Plake, Patrice A Frost, Sarah J Ratcliffe, Liping Wang, Eileen M Lafer, Ruth M Ruprecht
OBJECTIVE: Worldwide, most new HIV infections occur through mucosal exposure. Immunoglobulin M (IgM) is the first antibody class generated in response to infectious agents; IgM is present in the systemic circulation and in mucosal fluids as secretory IgM. We sought to investigate for the first time the role of IgM in preventing AIDS virus acquisition in vivo. DESIGN: Recombinant polymeric monoclonal IgM was generated from the neutralizing monoclonal IgG1 antibody 33C6-IgG1, tested in vitro, and given by passive intrarectal (i...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29758076/high-throughput-generation-and-characterization-of-replication-competent-clade-c-transmitter-founder-simian-human-immunodeficiency-viruses
#13
Debashis Dutta, Samuel Johnson, Alisha Dalal, Martin J Deymier, Eric Hunter, Siddappa N Byrareddy
Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV) and simian tropic HIV (stHIV). This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia...
2018: PloS One
https://www.readbyqxmd.com/read/29755620/human-genomic-loci-important-in-common-infectious-diseases-role-of-high-throughput-sequencing-and-genome-wide-association-studies
#14
REVIEW
Gerald Mboowa, Ivan Sserwadda, Marion Amujal, Norah Namatovu
HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs)...
2018: Canadian Journal of Infectious Diseases & Medical Microbiology
https://www.readbyqxmd.com/read/29753126/23-valent-pneumococcal-polysaccharide-vaccine-elicits-hierarchical-antibody-and-cellular-responses-in-healthy-and-tuberculosis-cured-elderly-and-hiv-1-infected-subjects
#15
Huichang Huang, Xiaohua Qian, Rong Pan, Ling Shen, Shanshan Liang, Feifei Wang, Peng Zhang, Hongbo Shen, Zheng W Chen
The PPV23 immunizes healthy elderly and other high-risk populations against pneumococcal disease. Immune mechanisms whereby these populations differently mount antibody(Ab) and cellular responses to PPV23 vaccination remain unknown. Here, healthy elderly, those elderly with prior tuberculosis-cured history (TB-cured), and HIV-infected humans were vaccinated with PPV23, and assessed for opsonophagocytic Ab responses and potential cellular mechanisms. PPV23 vaccination elicited hierarchical responses of opsonophagocytic Ab...
May 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29749878/audit-of-a-human-papillomavirus-vaccine-programme-for-men-who-have-sex-with-men-delivered-through-an-integrated-sexual-reproductive-health-service
#16
Carys Knapper, Humphrey Birley, Irene Parker
Following the Joint Committee on Vaccination and Immunisation statement in November 2015 advising a human papillomavirus (HPV) vaccination programme targeting men who have sex with men (MSM) up to the age of 45 attending Genitourinary medicine and HIV services, we launched a HPV vaccination programme for MSM to be delivered through our Integrated Sexual Reproductive Health drop-in service across Newport and the South East Wales Valleys from 1 August 2016. Over the first 18 months of the vaccination programme 539 of the 693 (77%) eligible MSM who attended clinics where the vaccine was available commenced vaccination...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29746590/structural-and-immunologic-correlates-of-chemically-stabilized-hiv-1-envelope-glycoproteins
#17
Torben Schiffner, Jesper Pallesen, Rebecca A Russell, Jonathan Dodd, Natalia de Val, Celia C LaBranche, David Montefiori, Georgia D Tomaras, Xiaoying Shen, Scarlett L Harris, Amin E Moghaddam, Oleksandr Kalyuzhniy, Rogier W Sanders, Laura E McCoy, John P Moore, Andrew B Ward, Quentin J Sattentau
Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects structure, antigenicity and immunogenicity is poorly understood and its use remains entirely empirical. We have solved the first cryo-EM structure of a cross-linked vaccine antigen. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a CD4 binding site-specific broadly neutralizing antibody (bNAb) Fab fragment reveals how cross-linking affects key properties of the trimer...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29743361/a-novel-strategy-to-adapt-shiv-e1-carrying-env-from-an-rv144-volunteer-to-rhesus-macaques-coreceptor-switch-and-final-recovery-of-a-pathogenic-virus-with-exclusive-r5-tropism
#18
Hanna B Scinto, Sandeep Gupta, Swati Thorat, Muhammad M Mukhtar, Anthony Griffiths, Jennifer Delgado, Elizabeth Plake, Hemant K Vyas, Amanda Strickland, Siddappa N Byrareddy, David C Montefiori, Celia LaBranche, Ranajit Pal, Jim Treece, Sharon Orndorff, Maria Grazia Ferrari, Deborah Weiss, Agnes-Laurence Chenine, Robert McLinden, Nelson Michael, Jerome H Kim, Merlin Robb, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Ruth M Ruprecht
The Phase III RV144 HIV vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clades A/E (CRF01_AE) predominate; in such viruses, env originates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carrying env isolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-κB sites, thus resembling HIV LTRs...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743003/high-prevalence-of-anti-hepatitis-a-igg-in-a-cohort-of-uk-hiv-negative-men-who-have-sex-with-men-implications-for-local-hepatitis-a-vaccine-policy
#19
A Bhagey, K Foster, S Ralph, A Wardropper, C White, V Wholey, S Duncan
BASHH guidelines recommend that 'the hepatitis A virus total antibody test can be offered to at-risk patients whose immune status is unknown … depending on local funding arrangements'. We sought to measure the local prevalence of anti-hepatitis A (HAV) IgG in HIV-negative men who have sex with men (MSM), to inform the utility of pre-vaccination screening. We assessed the prevalence of anti-HAV IgG in HIV-negative MSM who attended sexual health services in County Durham and Darlington, UK, from March to August 2017...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29742434/live-imaging-of-hiv-1-transfer-across-t-cell-virological-synapse-to-epithelial-cells-that-promotes-stromal-macrophage-infection
#20
Fernando Real, Alexis Sennepin, Yonatan Ganor, Alain Schmitt, Morgane Bomsel
During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4+ T cells and the epithelial cell mucosal surface...
May 8, 2018: Cell Reports
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