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Article ; Online: Complement contributes to antibody-mediated protection against repeated SHIV challenge.

Goldberg, Benjamin S / Spencer, David A / Pandey, Shilpi / Ordonez, Tracy / Barnette, Philip / Yu, Yun / Gao, Lina / Dufloo, Jérémy / Bruel, Timothée / Schwartz, Olivier / Ackerman, Margaret E / Hessell, Ann J

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 20, Page(s) e2221247120

Abstract: The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization ... ...

Abstract	The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization breadth and potency, it remains unclear whether augmenting the effector functions elicited by broadly neutralizing antibodies (bNAbs) may also improve their clinical potential. Among these effector functions, complement-mediated activities, which can culminate in the lysis of virions or infected cells, have been the least well studied. Here, functionally modified variants of the second-generation bNAb 10-1074 with ablated and enhanced complement activation profiles were used to examine the role of complement-associated effector functions. When administered prophylactically against simian-HIV challenge in rhesus macaques, more bNAb was required to prevent plasma viremia when complement activity was eliminated. Conversely, less bNAb was required to protect animals from plasma viremia when complement activity was enhanced. These results suggest that complement-mediated effector functions contribute to in vivo antiviral activity, and that their engineering may contribute to the further improvements in the efficacy of antibody-mediated prevention strategies.
MeSH term(s)	Animals ; HIV Infections ; Simian Acquired Immunodeficiency Syndrome ; Simian Immunodeficiency Virus ; Broadly Neutralizing Antibodies ; Macaca mulatta ; Viremia/prevention & control ; Complement System Proteins ; HIV Antibodies ; Antibodies, Neutralizing
Chemical Substances	Broadly Neutralizing Antibodies ; Complement System Proteins (9007-36-7) ; HIV Antibodies ; Antibodies, Neutralizing
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2221247120
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Article: The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine.

Research square

2024

Abstract: There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) ... ...

Abstract	There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have previously demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and improves vaccine immune responses
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-4139764/v1
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Article ; Online: Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines.

Weiss, Svenja / Itri, Vincenza / Pan, Ruimin / Jiang, Xunqing / Luo, Christina C / Morris, Lynn / Malherbe, Delphine C / Barnette, Philip / Alexander, Jeff / Kong, Xiang-Peng / Haigwood, Nancy L / Hessell, Ann J / Duerr, Ralf / Zolla-Pazner, Susan

Nature communications

2022 Volume 13, Issue 1, Page(s) 903

Abstract: V2p and V2i antibodies (Abs) that are specific for epitopes in the V1V2 region of the HIV gp120 envelope (Env) do not effectively neutralize HIV but mediate Fc-dependent anti-viral activities that have been correlated with protection from, or control of ... ...

Abstract	V2p and V2i antibodies (Abs) that are specific for epitopes in the V1V2 region of the HIV gp120 envelope (Env) do not effectively neutralize HIV but mediate Fc-dependent anti-viral activities that have been correlated with protection from, or control of HIV, SIV and SHIV infections. Here, we describe a novel molecular toolbox that allows the discrimination of antigenically and functionally distinct polyclonal V2 Ab responses. We identify different patterns of V2 Ab induction by SHIV infection and three separate vaccine regimens that aid in fine-tuning an optimized immunization protocol for inducing V2p and V2i Abs. We observe no, or weak and sporadic V2p and V2i Abs in non-vaccinated SHIV-infected NHPs, but strong V2p and/or V2i Ab responses after immunization with a V2-targeting vaccine protocol. The V2-focused vaccination is superior to both natural infection and to immunization with whole Env constructs for inducing functional V2p- and V2i-specific responses. Strikingly, levels of V2-directed Abs correlate inversely with Abs specific for peptides of V3 and C5. These data demonstrate that a V1V2-targeting vaccine has advantages over the imprecise targeting of SIV/SHIV infections and of whole Env-based immunization regimens for inducing a more focused functional V2p- and V2i-specific Ab response.
MeSH term(s)	AIDS Vaccines/immunology ; Animals ; Antibodies, Monoclonal/immunology ; Epitopes/immunology ; Female ; HIV Antibodies/blood ; HIV Envelope Protein gp120/immunology ; HIV-1/immunology ; Macaca mulatta ; Male ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/prevention & control ; Simian Immunodeficiency Virus/immunology ; Vaccination
Chemical Substances	AIDS Vaccines ; Antibodies, Monoclonal ; Epitopes ; HIV Antibodies ; HIV Envelope Protein gp120
Language	English
Publishing date	2022-02-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28450-1
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Article ; Online: Corrigendum: Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Hioe, Catarina E / Liu, Xiaomei / Banin, Andrew N / Heindel, Daniel W / Klingler, Je Romine / Rao, Priyanka G / Luo, Christina C / Jiang, Xunqing / Pandey, Shilpi / Ordonez, Tracy / Barnette, Philip / Totrov, Maxim / Zhu, Jiang / Na das, Arthur / Zolla-Pazner, Susan / Upadhyay, Chitra / Shen, Xiaoying / Kong, Xiang-Peng / Hessell, Ann J

Frontiers in immunology

2023 Volume 14, Page(s) 1329069

Abstract: This corrects the article DOI: 10.3389/fimmu.2023.1271686.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2023.1271686.].
Language	English
Publishing date	2023-11-09
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1329069
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Article ; Online: Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis.

Spencer, David A / Goldberg, Benjamin S / Pandey, Shilpi / Ordonez, Tracy / Dufloo, Jérémy / Barnette, Philip / Sutton, William F / Henderson, Heidi / Agnor, Rebecca / Gao, Lina / Bruel, Timothée / Schwartz, Olivier / Haigwood, Nancy L / Ackerman, Margaret E / Hessell, Ann J

Nature communications

2022 Volume 13, Issue 1, Page(s) 662

Abstract: Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear ... ...

Abstract	Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C') activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78-88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C' functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIV
MeSH term(s)	Animals ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Antibody-Dependent Cell Cytotoxicity/immunology ; Broadly Neutralizing Antibodies/immunology ; Broadly Neutralizing Antibodies/metabolism ; Broadly Neutralizing Antibodies/pharmacology ; Cell Line, Tumor ; Complement System Proteins/immunology ; Complement System Proteins/metabolism ; Cytokines/immunology ; Cytokines/metabolism ; Female ; HIV Antibodies/immunology ; HIV Antibodies/metabolism ; HIV Antibodies/pharmacology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/immunology ; HIV-1/physiology ; Humans ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Macaca mulatta ; Male ; Phagocytosis/drug effects ; Phagocytosis/immunology ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/prevention & control ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/drug effects ; Simian Immunodeficiency Virus/immunology ; Simian Immunodeficiency Virus/physiology ; Viremia/blood ; Viremia/immunology ; Viremia/prevention & control
Chemical Substances	Broadly Neutralizing Antibodies ; Cytokines ; HIV Antibodies ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2022-02-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28250-7
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Article ; Online: Evidence for the Role of a Second Fc-Binding Receptor in Placental IgG Transfer in Nonhuman Primates.

Rosenberg, Yvonne J / Ordonez, Tracy / Khanwalkar, Urjeet S / Barnette, Philip / Pandey, Shilpi / Backes, Iara M / Otero, Claire E / Goldberg, Benjamin S / Crowley, Andrew R / Leib, David A / Shapiro, Mariya B / Jiang, Xiaoming / Urban, Lori A / Lees, Jonathan / Hessell, Ann J / Permar, Sallie / Haigwood, Nancy L / Ackerman, Margaret E

mBio

2023 Volume 14, Issue 2, Page(s) e0034123

Abstract: Transplacental transfer of maternal antibodies provides the fetus and newborn with passive protection against infectious diseases. While the role of the highly conserved neonatal Fc receptor (FcRn) in transfer of IgG in mammals is undisputed, recent ... ...

Abstract	Transplacental transfer of maternal antibodies provides the fetus and newborn with passive protection against infectious diseases. While the role of the highly conserved neonatal Fc receptor (FcRn) in transfer of IgG in mammals is undisputed, recent reports have suggested that a second receptor may contribute to transport in humans. We report poor transfer efficiency of plant-expressed recombinant HIV-specific antibodies, including engineered variants with high FcRn affinity, following subcutaneous infusion into rhesus macaques close to parturition. Unexpectedly, unlike those derived from mammalian tissue culture, plant-derived antibodies were essentially unable to cross macaque placentas. This defect was associated with poor Fcγ receptor binding and altered Fc glycans and was not recapitulated in mice. These results suggest that maternal-fetal transfer of IgG across the three-layer primate placenta may require a second receptor and suggest a means of providing maternal antibody treatments during pregnancy while avoiding fetal harm.
MeSH term(s)	Pregnancy ; Female ; Mice ; Humans ; Animals ; Placenta ; Maternal-Fetal Exchange ; Macaca mulatta ; Immunoglobulin G ; Receptors, Fc/metabolism ; Antibodies, Monoclonal/metabolism ; Histocompatibility Antigens Class I ; HIV Infections/metabolism ; Mammals/metabolism
Chemical Substances	Immunoglobulin G ; Receptors, Fc ; Antibodies, Monoclonal ; Histocompatibility Antigens Class I
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00341-23
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Article ; Online: Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.

Hioe, Catarina E / Liu, Xiaomei / Banin, Andrew N / Heindel, Daniel W / Klingler, Jéromine / Rao, Priyanka G / Luo, Christina C / Jiang, Xunqing / Pandey, Shilpi / Ordonez, Tracy / Barnette, Philip / Totrov, Maxim / Zhu, Jiang / Nádas, Arthur / Zolla-Pazner, Susan / Upadhyay, Chitra / Shen, Xiaoying / Kong, Xiang-Peng / Hessell, Ann J

Frontiers in immunology

2023 Volume 14, Page(s) 1271686

Abstract: Introduction: Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an ... ...

Abstract	Introduction: Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge. Objective: This study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env). Methods: Four groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope Results: Rabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses. Conclusion: These data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.
MeSH term(s)	Animals ; Rabbits ; HIV Infections ; HIV Antibodies ; Antigen-Antibody Complex ; HIV-1 ; Vaccines, DNA ; Vaccination ; Antibodies, Neutralizing ; HIV Seropositivity ; Epitopes ; DNA
Chemical Substances	HIV Antibodies ; Antigen-Antibody Complex ; Vaccines, DNA ; Antibodies, Neutralizing ; Epitopes ; DNA (9007-49-2)
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1271686
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Article ; Online: Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor.

Spencer, David A / Malherbe, Delphine C / Vázquez Bernat, Néstor / Ádori, Monika / Goldberg, Benjamin / Dambrauskas, Nicholas / Henderson, Heidi / Pandey, Shilpi / Cheever, Tracy / Barnette, Philip / Sutton, William F / Ackerman, Margaret E / Kobie, James J / Sather, D Noah / Karlsson Hedestam, Gunilla B / Haigwood, Nancy L / Hessell, Ann J

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 206, Issue 5, Page(s) 999–1012

Abstract: Vaccine efforts to combat HIV are challenged by the global diversity of viral strains and shielding of neutralization epitopes on the viral envelope glycoprotein trimer. Even so, the isolation of broadly neutralizing Abs from infected individuals ... ...

Abstract	Vaccine efforts to combat HIV are challenged by the global diversity of viral strains and shielding of neutralization epitopes on the viral envelope glycoprotein trimer. Even so, the isolation of broadly neutralizing Abs from infected individuals suggests the potential for eliciting protective Abs through vaccination. This study reports a panel of 58 mAbs cloned from a rhesus macaque (
MeSH term(s)	AIDS Vaccines/immunology ; Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Binding Sites/immunology ; Cell Line ; Epitopes/immunology ; HIV Antibodies/immunology ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Immunization/methods ; Immunoglobulin Variable Region/immunology ; Macaca mulatta/immunology ; THP-1 Cells/immunology ; Vaccination/methods ; Viral Envelope Proteins/immunology ; env Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; Immunoglobulin Variable Region ; Viral Envelope Proteins ; env Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2001082
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques.

Sarkar, Sanghita / Spencer, David A / Barnette, Philip / Pandey, Shilpi / Sutton, William F / Basu, Madhubanti / Burch, Reuben E / Cleveland, John D / Rosenberg, Alexander F / Rangel-Moreno, Javier / Keefer, Michael C / Hessell, Ann J / Haigwood, Nancy L / Kobie, James J

Frontiers in immunology

2021 Volume 12, Page(s) 757811

Abstract: Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T ... ...

Abstract	Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 plasmids and gp140 trimeric proteins derived from an HIV-1 infected subject that developed bNAbs, we determined the characteristics of the Env-specific humoral response in vaccinated rhesus macaques in the context of CD4+ T cell depletion. Unexpectedly, both CD4+ depleted and non-depleted animals developed comparable Tier 1 and 2 heterologous HIV-1 neutralizing plasma antibody titers. There was no deficit in protection from SHIV challenge, no diminution of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis, or antibody-dependent complement deposition in the CD4+ depleted animals. These collective results suggest that in the presence of diminished CD4+ T cell help, HIV neutralizing antibodies were still generated, which may have implications for developing effective HIV vaccine strategies.
MeSH term(s)	AIDS Vaccines ; Animals ; Antibodies, Bacterial/biosynthesis ; Antibodies, Bacterial/immunology ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity ; Broadly Neutralizing Antibodies/biosynthesis ; Broadly Neutralizing Antibodies/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cross Reactions ; Female ; Germinal Center/immunology ; HIV Antibodies/biosynthesis ; HIV Antibodies/immunology ; HIV Envelope Protein gp160/immunology ; HIV-1/immunology ; Immunization, Secondary ; Macaca mulatta/immunology ; Male ; Phagocytosis ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/prevention & control ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/immunology ; Vaccine Development ; Vaccines, Synthetic ; Viral Load ; env Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Antibodies, Bacterial ; Antibodies, Viral ; Broadly Neutralizing Antibodies ; HIV Antibodies ; HIV Envelope Protein gp160 ; Vaccines, Synthetic ; env Gene Products, Human Immunodeficiency Virus ; gp140 envelope protein, Human immunodeficiency virus 1 ; gp160 protein, Human immunodeficiency virus 1
Language	English
Publishing date	2021-10-20
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.757811
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Article ; Online: Modified Adenovirus Prime-Protein Boost Clade C HIV Vaccine Strategy Results in Reduced Viral DNA in Blood and Tissues Following Tier 2 SHIV Challenge.

Frontiers in immunology

2021 Volume 11, Page(s) 626464

Abstract: Designing immunogens and improving delivery methods eliciting protective immunity is a paramount goal of HIV vaccine development. A comparative vaccine challenge study was performed in rhesus macaques using clade C HIV Envelope (Env) and SIV Gag antigens. ...

Abstract	Designing immunogens and improving delivery methods eliciting protective immunity is a paramount goal of HIV vaccine development. A comparative vaccine challenge study was performed in rhesus macaques using clade C HIV Envelope (Env) and SIV Gag antigens. One group was vaccinated using co-immunization with DNA Gag and Env expression plasmids cloned from a single timepoint and trimeric Env gp140 glycoprotein from one of these clones (DNA+Protein). The other group was a prime-boost regimen composed of two replicating simian (SAd7) adenovirus-vectored vaccines expressing Gag and one Env clone from the same timepoint as the DNA+Protein group paired with the same Env gp140 trimer (SAd7+Protein). The env genes were isolated from a single pre-peak neutralization timepoint approximately 1 year post infection in CAP257, an individual with a high degree of neutralization breadth. Both DNA+Protein and SAd7+Protein vaccine strategies elicited significant Env-specific T cell responses, lesser Gag-specific responses, and moderate frequencies of Env-specific T
MeSH term(s)	AIDS Vaccines/immunology ; AIDS Vaccines/pharmacology ; Adenoviridae ; Animals ; DNA, Viral/blood ; DNA, Viral/immunology ; HIV Antibodies/blood ; HIV Antibodies/immunology ; HIV Infections/blood ; HIV Infections/immunology ; HIV Infections/prevention & control ; Immunization, Secondary ; Immunoglobulin A/blood ; Immunoglobulin A/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Macaca mulatta ; Male
Chemical Substances	AIDS Vaccines ; DNA, Viral ; HIV Antibodies ; Immunoglobulin A ; Immunoglobulin G
Language	English
Publishing date	2021-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.626464
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