The Experts below are selected from a list of 59742 Experts worldwide ranked by ideXlab platform
David C Montefiori - One of the best experts on this subject based on the ideXlab platform.
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rapid boosting of hiv 1 Neutralizing Antibody responses in humans following a prolonged immunologic rest period
The Journal of Infectious Diseases, 2019Co-Authors: Paul Spearman, Ying Huang, David C Montefiori, Georgia D Tomaras, Marnie Elizaga, Guido Ferrari, Munir S Alam, Abby Isaacs, Hasan Ahmed, John HuralAbstract:Background The durability and breadth of human immunodeficiency virus type 1 (HIV-1)-specific immune responses elicited through vaccination are important considerations in the development of an effective HIV-1 vaccine. Responses to HIV-1 envelope subunit protein (Env) immunization in humans are often described as short-lived. Methods We enrolled 16 healthy volunteers who had received priming with an HIV-1 subtype B Env vaccine given with MF59 adjuvant 5-17 years previously and 20 healthy unprimed volunteers. Three booster immunizations with a heterologous subtype C trimeric gp140 protein vaccine were administered to the primed group, and the same subtype C gp140 protein vaccination regimen was administered to the unprimed subjects. Results Binding antibodies and Neutralizing antibodies to tier 1 viral isolates were detected in the majority of previously primed subjects. Remarkably, a single dose of protein boosted binding and Neutralizing Antibody titers in 100% of primed subjects following this prolonged immunologic rest period, and CD4+ T-cell responses were boosted in 75% of primed individuals. Conclusions These results demonstrate that HIV-1 protein immunogens can elicit durable memory T- and B-cell responses and that strong tier 1 virus Neutralizing responses can be elicited by a single booster dose of protein following a long immunologic rest period. However, we found no evidence that cross-clade boosting led to a significantly broadened Neutralizing Antibody response.
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comparison of Neutralizing Antibody responses elicited from highly diverse polyvalent heterotrimeric hiv 1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques
PLOS ONE, 2014Co-Authors: Emma J Bowles, Torben Schiffner, Maximillian Rosario, Gemma A Needham, Meghna Ramaswamy, Joanna F Mcgouran, Benedikt M Kessler, Celia C Labranche, Andrew J Mcmichael, David C MontefioriAbstract:Eliciting Neutralizing antibodies capable of inactivating a broad spectrum of HIV-1 strains is a major goal of HIV-1 vaccine design. The challenge is that envelopes (Envs) of circulating viruses are almost certainly different from any Env used in a vaccine. A novel immunogen composed of a highly diverse set of gp140 Envs including subtypes A, B, C, D and F was developed to stimulate a more cross-Neutralizing Antibody response. Env heterotrimers composed of up to 54 different gp140s were produced with the aim of focusing the response to the conserved regions of Env while reducing the dominance of any individual hypervariable region. Heterotrimeric gp140 Envs of inter- and intra-subtype combinations were shown to bind CD4 and a panel of Neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140. Macaques immunized with six groups of heterotrimer mixtures showed slightly more potent Neutralizing Antibody responses in TZM-BL tier 1 and A3R5 tier 2 pseudovirus assays than macaques immunized with monovalent Env gp140, and exhibited a marginally greater focus on the CD4-binding site. Carbopol enhanced neutralization when used as an adjuvant instead of RIBI in combination with UG37 gp140. These data indicate that cross-subtype heterotrimeric gp140 Envs may elicit some improvement of the Neutralizing Antibody response in macaques compared to monovalent gp140 Env.
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aiming to induce broadly reactive Neutralizing Antibody responses with hiv 1 vaccine candidates
Expert Review of Vaccines, 2006Co-Authors: Barton F Haynes, David C MontefioriAbstract:Neutralizing Antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective Neutralizing Antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1.
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Neutralizing Antibody independent containment of immunodeficiency virus challenges by dna priming and recombinant pox virus booster immunizations
Nature Medicine, 1999Co-Authors: Harriet L Robinson, David C Montefiori, R P Johnson, Kelledy Manson, M L Kalish, J D Lifson, Tahir A Rizvi, Gail P Mazzara, Dennis Panicali, James G HerndonAbstract:Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require Neutralizing Antibody and was active for a series of challenges ending with a highly virulent virus with a primary isolate envelope heterologous to the immunizing strain.
John V. Williams - One of the best experts on this subject based on the ideXlab platform.
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structure of the human metapneumovirus fusion protein with Neutralizing Antibody identifies a pneumovirus antigenic site
Nature Structural & Molecular Biology, 2012Co-Authors: Xiaolin Wen, Reagan G Cox, George P Leser, Robert A Lamb, Jens C. Krause, John V. WilliamsAbstract:The crystal structure of the fusion protein from human metapneumovirus in complex with a potently Neutralizing Antibody reveals a novel antigenic site, which could be explored to develop vaccines against this and related paramyxoviruses.
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Structure of the human metapneumovirus fusion protein with Neutralizing Antibody identifies a pneumovirus antigenic site.
2012Co-Authors: Xiaolin Wen, Reagan G Cox, James E Crowe, George P Leser, Robert A Lamb, Jens C. Krause, John V. Williams, Theodore S. JardetzkyAbstract:Human metapneumovirus and respiratory syncytial virus cause lower respiratory tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the Neutralizing Antibody response. Here we show that a potently Neutralizing anti-human metapneumovirus Antibody (DS7) binds a structurally invariant domain of F, revealing a new epitope that could be targeted in vaccine development.
Yiming Shao - One of the best experts on this subject based on the ideXlab platform.
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broad hiv 1 Neutralizing Antibody response induced by heterologous gp140 gp145 dna prime vaccinia boost immunization
Vaccine, 2012Co-Authors: Lianxing Liu, Yanling Hao, Z D Luo, Yang Huang, Ying Liu, Yiming ShaoAbstract:Abstract Objective To develop an effective HIV vaccine strategy that can induce cross-reactive Neutralizing Antibody. Methods Codon-optimized gp140 and gp145 env genes derived from HIV-1 cn54 , a CRF07 B′/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-γ ELISPOT assay. A panel of primary isolates of clade B′ and B′/C HIV-1 and TZM-bl cells was used to determine the Neutralizing activity of immunized sera. Results The Neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B′ and B′/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best Neutralizing Antibody response with a broad Neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145 + gp145 homologous prime-boost. Conclusions This heterologous prime-boost immunization strategy could be used to design immunogen-generating broad Neutralizing antibodies against genetic variance pathogens.
Robert R Redfield - One of the best experts on this subject based on the ideXlab platform.
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correlation between circulating hiv 1 rna and broad hiv 1 Neutralizing Antibody activity
Journal of Acquired Immune Deficiency Syndromes, 2011Co-Authors: Mohammad M Sajadi, Yongjun Guan, Anthony L Devico, Michael S Seaman, Mian B Hossain, George K Lewis, Robert R RedfieldAbstract:Objective: To examine the relationship between HIV-1 antigenic load (plasma RNA copies/mL) and broad HIV-1 Neutralizing Antibody activity. Methods: Plasma from 120 HIV-1―infected patients, including HIV-1 natural viral suppressors (similar to elite controllers), was tested for neutralization against 15 Tier 1/Tier 2 HIV-1 pseudoviruses. Broad HIV-1 Neutralizing Antibody activity was confirmed with immunoglobulin G and heterlogous clade testing (18 pseudoviruses from Clades A, C, and CRF02_AG). Statistical analysis was performed to determine factors associated with broad HIV-1 Neutralizing Antibody activity. Results: Ten individuals with broad HIV-1 Neutralizing Antibody activity were identified. These individuals had a median CD4 count of 589 cells per microliter (range 202-927), 1611 HIV-1 RNA copies per milliliter (range 110―8964), and 13 years since HIV diagnosis (range 1-22). There was a significant correlation between the presence of broadly Neutralizing antibodies in those with HIV-1 RNA between 100 and 10,000 copies per milliliter compared with those 10,000 copies per milliliter (P = 0.0003 and 0.0245, respectively). Individuals with HIV-1 RNA 100-10,000 copies per milliliter had a higher number of Tier 2 viruses neutralized compared with the 10,000 copies per milliliter groups (P ≤ 0.0001 and P = 0.076, respectively). Male sex was associated with broad HIV-1 Neutralizing Antibody activity (P = 0.016). Conclusions: These results indicate that low but persistent HIV antigen expression correlates with broad HIV-1 Neutralizing Antibody activity. At higher levels of plasma viremia, neutralization titers were diminished. Conversely, at lower levels, there seems to be insufficient antigen stimulation to maintain high neutralization titers. These findings may have important implications in furthering the understanding of the humoral response to HIV infection.
Christos J Petropoulos - One of the best experts on this subject based on the ideXlab platform.
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Neutralizing Antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus hiv infection evidence for a constraint on the ability of hiv to completely evade Neutralizing Antibody responses
Journal of Virology, 2006Co-Authors: Steven G Deeks, Terri Wrin, Justin Galovich, Becky Schweighardt, Rebecca Hoh, Elizabeth Sinclair, Peter W Hunt, Joseph M Mccune, Jeffrey N Martin, Christos J PetropoulosAbstract:Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization Antibody escape. We therefore measured Neutralizing Antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing Antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of Neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of Neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher Neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, Neutralizing Antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of Neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the Neutralizing Antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.
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Neutralizing Antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent hiv infection
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Simon D W Frost, Davey M. Smith, Sergei Kosakovsky L Pond, Terri Wrin, Yang Liu, Ellen E Paxinos, Colombe Chappey, Justin Galovich, Jeff Beauchaine, Christos J PetropoulosAbstract:HIV type 1 (HIV-1) can rapidly escape from Neutralizing Antibody responses. The genetic basis of this escape in vivo is poorly understood. We compared the pattern of evolution of the HIV-1 env gene between individuals with recent HIV infection whose virus exhibited either a low or a high rate of escape from Neutralizing Antibody responses. We demonstrate that the rate of viral escape at a phenotypic level is highly variable among individuals, and is strongly correlated with the rate of amino acid substitutions. We show that dramatic escape from Neutralizing antibodies can occur in the relative absence of changes in glycosylation or insertions and deletions (“indels”) in the envelope; conversely, changes in glycosylation and indels occur even in the absence of Neutralizing Antibody responses. Comparison of our data with the predictions of a mathematical model support a mechanism in which escape from Neutralizing antibodies occurs via many amino acid substitutions, with low cross-neutralization between closely related viral strains. Our results suggest that autologous Neutralizing Antibody responses may play a pivotal role in the diversification of HIV-1 envelope during the early stages of infection.
