A phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C adeno-associated virus vaccine.

Abstract:

:A novel prophylactic AIDS vaccine candidate, consisting of single-stranded DNA for HIV-1 subtype C gag, protease, and part of reverse transcriptase genes, enclosed within a recombinant adeno-associated virus serotype-2 protein capsid (tgAAC09) induced T cell responses and antibodies in nonhuman primates. In this randomized, dose escalation phase I trial, HIV-uninfected healthy volunteers (50 in Europe, 30 in India) received a single intramuscular injection of tgAAC09 at 3 x 10(9) DNase resistant particles (DRP) (n = 16), 3 x 10(10) DRP (n = 23), 3 x 10(11) DRP (n = 25), or placebo (n = 16). Twenty-one participants in Europe received a second (boost) dose of 3 x 10(11) DRP tgAAC09 or placebo at least 24 weeks after the first injection. The vaccine was safe and well-tolerated after initial and boost vaccination. Local and systemic reactogenicity was experienced by 13-25% of participants and was not dose related. No vaccine-related serious adverse events were reported. Modest HIV-specific T cell responses were detected in 7/64 vaccinees (40-385 SFC/10(6) PBMC), with 16% (4/25) responders in the highest dose group. All responses were to Gag epitopes. tgAAC09 appears to be safe, well-tolerated, and modestly immunogenic. Further evaluation of higher doses of tgAAC09 and boost injections is ongoing in Africa.

authors

Mehendale S,van Lunzen J,Clumeck N,Rockstroh J,Vets E,Johnson PR,Anklesaria P,Barin B,Boaz M,Kochhar S,Lehrman J,Schmidt C,Peeters M,Schwarze-Zander C,Kabamba K,Glaunsinger T,Sahay S,Thakar M,Paranjape R,Gilmour J,

doi

10.1089/aid.2007.0292

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

873-80

issue

6

eissn

0889-2229

issn

1931-8405

journal_volume

24

pub_type

杂志文章,随机对照试验
  • HTLV type 1 infection in squirrel monkeys (Saimiri sciureus): a promising animal model for HTLV type 1 human infection.

    abstract::We show that the squirrel monkey Saimiri sciureus is susceptible to experimental infection with either syngeneic or allogeneic HTLV-1-immortalized cells. As in humans, such experimental inoculation leads to chronic infection, and HTLV-1 provirus was detected in PBMCs by PCR. Chronically infected monkeys developed high...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,评审

    doi:10.1089/08892220050193245

    authors: Kazanji M

    更新日期:2000-11-01 00:00:00

  • Comparison of once-daily fosamprenavir boosted with either 100 or 200 mg of ritonavir, in combination with abacavir/lamivudine: 96-week results from COL100758.

    abstract::The long-term efficacy of once-daily (qd) fosamprenavir (FPV) 1400 mg boosted by ritonavir 100 mg (FPV/r100) has not been evaluated previously. A 96-week open-label, randomized, multicenter study compared the efficacy/safety of FPV/r100 with FPV 1400 mg boosted by ritonavir 200 mg qd (FPV/r200), plus abacavir/lamivudi...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1089/aid.2008.0231

    authors: Hicks CB,DeJesus E,Sloan LM,Sension MG,Wohl DA,Liao Q,Ross LL,Pakes GE,Pappa KA,Lancaster CT,COL100758 Study Team.

    更新日期:2009-04-01 00:00:00

  • Serum albumin as a prognostic indicator for HIV disease progression.

    abstract::Low albumin levels have been associated with HIV progression. The objective of this analysis was to confirm this association and to further examine the effect of albumin before and after HIV seroconversion on disease progression. The association was first examined among individuals already infected with HIV at entry i...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2006.22.14

    authors: Mehta SH,Astemborski J,Sterling TR,Thomas DL,Vlahov D

    更新日期:2006-01-01 00:00:00

  • Human T cell lymphotropic virus type I (HTLV-I) p12I is dispensable for HTLV-I transmission and maintenance of infection in vivo.

    abstract::The function of the p12(I) protein of human T cell lymphotropic virus type I (HTLV-I) has been under debate. p12K (lysine) and p12R (arginine) variants of this protein at amino acid 88 and a shorter life of p12K had been reported by another group. Because HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2004.20.1092

    authors: Furukawa Y,Usuku K,Izumo S,Osame M

    更新日期:2004-10-01 00:00:00

  • Frequent and early in utero HIV-1 infection.

    abstract::We have investigated in utero human immunodeficiency virus type 1 (HIV-1) transmission by analyzing human fetal tissues for the presence of viral DNA by means of the polymerase chain reaction (PCR). Thirty three fetal samples: thymus, spleen, and peripheral mononuclear blood cells (PMBC) were obtained at abortion (16 ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1991.7.337

    authors: Courgnaud V,Lauré F,Brossard A,Bignozzi C,Goudeau A,Barin F,Bréchot C

    更新日期:1991-03-01 00:00:00

  • Genetic characterization of HIV type 1 Nef-induced vesicle secretion.

    abstract::The HIV-1 Nef protein is known to be secreted, and our group has shown that Nef is secreted from nef-transfected and HIV-1-infected cells in small exosome-like vesicles (d. 40-100 nm). The role of secreted Nef remains to be fully characterized. Thus, it is important to characterize the nature of and the mechanisms reg...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2009.0068

    authors: Ali SA,Huang MB,Campbell PE,Roth WW,Campbell T,Khan M,Newman G,Villinger F,Powell MD,Bond VC

    更新日期:2010-02-01 00:00:00

  • Virus threshold determines disease in SIVsmmPBj14-infected macaques.

    abstract::Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtai...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922299311600

    authors: O'Neil SP,Mossman SP,Maul DH,Hoover EA

    更新日期:1999-01-20 00:00:00

  • Identification of mutations in proviral long terminal repeats of HIV type 1-infected subjects naive to drug therapy.

    abstract::Human immunodeficiency virus type 1 (HIV-1) proviral DNA sequences in the 5' long terminal repeat (LTR) were examined among 28 drug-naive individuals. Twenty-four subjects had highly conserved LTR sequences, however, more significant changes were observed in the remaining four LTR sequences. These included a 9-bp dele...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2004.20.1019

    authors: Copeland KF,Chen Z,Fiebig M,Ni L,Savoy S,Smaill FM,Rosenthal KL,Kim JE

    更新日期:2004-09-01 00:00:00

  • Genotypic characterization and comparison of full-length envelope glycoproteins from South African HIV type 1 subtype C primary isolates that utilize CCR5 and/or CXCR4.

    abstract::CCR5 has preferentially been used by all circulating HIV-1 subtype C viruses for cell entry. Recently, we reported the highest proportion of CXCR4-utilizing primary isolates among a cohort of 20 South African AIDS patients. This study describes and compares the Env genotypic characteristics from these 20 HIV-1 subtype...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2007.0304

    authors: Michler K,Connell BJ,Venter WD,Stevens WS,Capovilla A,Papathanasopoulos MA

    更新日期:2008-05-01 00:00:00

  • Conserved immunogenic region of a major core protein (p24) of human and simian immunodeficiency viruses.

    abstract::A murine monoclonal antibody (MoAb), VAK 4, has been known to specifically react with a major core protein (p24) as well as with its precursor (p55-57) and intermediate precursor (p40) of human immunodeficiency virus strain IIIB (HTLV-IIIB). Radioimmunoprecipitation assays revealed that VAK 4 MoAb precipitated a major...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1988.4.409

    authors: Koito A,Hattori T,Matsushita S,Maeda Y,Nozaki C,Sagawa K,Takatsuki K

    更新日期:1988-12-01 00:00:00

  • Reduced Expression of Siglec-7, NKG2A, and CD57 on Terminally Differentiated CD56-CD16+ Natural Killer Cell Subset Is Associated with Natural Killer Cell Dysfunction in Chronic HIV-1 Clade C Infection.

    abstract::HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status, and phenotypic alterations based on expression of inhibitory and activating receptors on NK ce...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2017.0095

    authors: Zulu MZ,Naidoo KK,Mncube Z,Jaggernath M,Goulder PJR,Ndung'u T,Altfeld M,Thobakgale CF

    更新日期:2017-12-01 00:00:00

  • The relationship between HIV type 1 disease progression and V3 serotype in a rural Ugandan cohort.

    abstract::Antigenic properties of the V3 region are reflected by HIV-1 serotypes. These may represent biological properties of the virus. We serotyped HIV-1 in 142 serum samples from participants in a rural Uganda cohort who seroconverted between August 1991 and December 2001. Clinical progression was assessed using Cox proport...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2004.20.932

    authors: Senkaali D,Muwonge R,Morgan D,Yirrell D,Whitworth J,Kaleebu P

    更新日期:2004-09-01 00:00:00

  • Partial purification of native HIV transmembrane protein gp41: generation of polyclonal and monoclonal antibodies.

    abstract::We partially purified the human immunodeficiency virus (HIV) glycoprotein gp41 from infected H9 cells by immunoaffinity chromatography using a column containing the M25 monoclonal antibody (diMarzo-Veronese et al., 1985). A pH 11.5 buffer worked best for eluting the glycoprotein from this column. The eluted gp41 was u...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1988.4.51

    authors: Zweig M,Showalter SD,Bladen SV,Gilden RV,Arthur LO,Robey WG,Nara PL,Fischinger PJ

    更新日期:1988-02-01 00:00:00

  • Response to nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-infected children with perinatal exposure to single-dose nevirapine.

    abstract::We set out to investigate whether there are clinically significant consequences when children with perinatal exposure to single-dose nevirapine are initiated on a nonnucleoside reverse transcriptase inhibitor (NNRTI) containing a highly active antiretroviral therapy (HAART) regimen. We carried out a chart and database...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2009.0054

    authors: Musiime V,Ssali F,Kayiwa J,Namala W,Kizito H,Kityo C,Mugyenyi P

    更新日期:2009-10-01 00:00:00

  • Transcriptional control of HIV replication by multiple modulators and their implication for a novel antiviral therapy.

    abstract::Transcriptional regulation is critical for the human immunodeficiency virus 1 (HIV-1) life cycle and is the only step at which the virus amplifies the content of its genetic information. Numerous known and still unknown transcriptional factors, both host and viral, regulate HIV-1 gene expression and latency. This arti...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,评审

    doi:10.1089/AID.2011.0263

    authors: Victoriano AF,Okamoto T

    更新日期:2012-02-01 00:00:00

  • Characterization of HIV-1 CRF01_AE env Genes Derived from Recently Infected Indonesian Individuals.

    abstract::To eradicate human immunodeficiency virus type 1 (HIV-1) infection, a comprehensive strategy including preventive vaccine development is needed. Envelope glycoproteins (Env) play a central role in viral infection and are the major targets of humoral immune responses. Therefore, Env is a candidate vaccine antigen, and ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2019.0179

    authors: Sasaki M,Kotaki T,Khairunisa SQ,Tachibana S,Ophinni Y,Hayashi Y,Nasronudin,Kameoka M

    更新日期:2020-03-01 00:00:00

  • Neuropathogenic SIVsmmFGb genetic diversity and selection-induced tissue-specific compartmentalization during chronic infection and temporal evolution of viral genes in lymphoid tissues and regions of the central nervous system.

    abstract::SIVsmmFGb is a lentivirus swarm that induces neuropathology in over 90% of infected pigtailed macaques and reliably models central nervous system HIV infection in people. We have previously studied SIVsmmFGb genetic diversity and compartmentalization during acute infection, but little is understood about diversity and...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2009.0168

    authors: Reeve AB,Pearce NC,Patel K,Augustus KV,Novembre FJ

    更新日期:2010-06-01 00:00:00

  • Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.

    abstract::Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1992.8.245

    authors: Doppler C,Schalasta G,Amtmann E,Sauer G

    更新日期:1992-02-01 00:00:00

  • Evaluation of primary resistance to HIV entry inhibitors among brazilian patients failing reverse transcriptase/protease inhibitors treatment reveal high prevalence of maraviroc resistance-related mutations.

    abstract::Entry inhibitor is a new class of drugs that target the viral envelope protein. This region is variable; hence resistance to these drugs may be present before treatment. The aim of this study was to analyze the frequency of patients failing treatment with transcriptase reverse and protease inhibitors that would respon...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2010.0057

    authors: Alencar CS,Nishiya AS,Ferreira S,Giret MT,Diaz RS,Sabino EC

    更新日期:2010-12-01 00:00:00

  • HIV-1 Very Low Level Viremia Is Associated with Virological Failure in Highly Active Antiretroviral Treatment-Treated Patients.

    abstract::The aim of this study was to evaluate the impact of HIV-1 very low-level viremia (<50 copies/ml) on the 2-year risk of virological failure. A retrospective analysis including HIV-positive patients presenting two consecutive HIV RNA below 50 copies/ml (outpatient clinic in Italy, first semester of 2010) was performed. ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2015.0102

    authors: Calcagno A,Motta I,Ghisetti V,Lo Re S,Allice T,Marinaro L,Milia MG,Tettoni MC,Trentini L,Orofino G,Salassa B,Di Perri G,Bonora S

    更新日期:2015-10-01 00:00:00

  • Helper and cytotoxic T cell responses of HIV type 1-infected individuals to synthetic peptides of HIV type 1 Rev.

    abstract::In cell-mediated immunity T cells recognize peptide fragments of the antigenic protein in association with major histocompatibility complex (MHC) proteins. Synthetic 9- to 16-mer peptides have been widely used to identify the region(s) of a protein that act as T cell epitope. Here, we report antigenic peptides identif...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1995.11.1335

    authors: Blazevic V,Ranki A,Krohn KJ

    更新日期:1995-11-01 00:00:00

  • Pharmacokinetics and pharmacodynamics in HIV prevention; current status and future directions: a summary of the DAIDS and BMGF sponsored think tank on pharmacokinetics (PK)/pharmacodynamics (PD) in HIV prevention.

    abstract::Thirty years after its beginning, the HIV/AIDS epidemic is still raging around the world. According to UNAIDS, in 2011 alone 1.7M deaths were attributable to AIDS, and 2.5M people were newly infected by the virus. Despite the success in treating HIV-infected people with potent antiretroviral drugs, preventing HIV infe...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,评审

    doi:10.1089/aid.2013.0122

    authors: Romano J,Kashuba A,Becker S,Cummins J,Turpin J,Veronese F,Antiretroviral Pharmacology In HIV Prevention Think Tank Participants.

    更新日期:2013-11-01 00:00:00

  • Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation.

    abstract::Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1991.7.521

    authors: Lifson JD,Rausch DM,Kalyanaraman VS,Hwang KM,Eiden LE

    更新日期:1991-06-01 00:00:00

  • Impact of sampling density on the extent of HIV clustering.

    abstract::Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2014.0173

    authors: Novitsky V,Moyo S,Lei Q,DeGruttola V,Essex M

    更新日期:2014-12-01 00:00:00

  • HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission.

    abstract::The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2015.0040

    authors: Collins-Fairclough AM,Dennis AM,Nelson JA,Weir SS,Figueroa JP

    更新日期:2015-08-01 00:00:00

  • Short communication: new HIV infections at Southern New England academic institutions: implications for prevention.

    abstract::New HIV infections among younger men who have sex with men (MSM) in the United States are escalating. Data on HIV infections in college students are limited. In 2010, three MSM college students presented to our clinic with primary HIV infection (PHI) in a single month. To determine the number of college students among...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2012.0130

    authors: Chan PA,Kazi S,Rana A,Blazar I,Dejong CC,Mayer KH,Huard TK,Carleton K,Gillani F,Alexander N,Parillo Z,Flanigan TP,Kantor R

    更新日期:2013-01-01 00:00:00

  • Near full-length genome characterization of HIV type 1 unique BC recombinant forms from Southern Brazil.

    abstract::Abstract In southern Brazil, CRF31_BC is the major HIV-1 recombinant form and URFs_BC occurs very infrequently. The near full-length genomes of four samples displaying a similar recombination profile in the integrase region and different profiles in the protease/reverse transcriptase regions were analyzed to elucidate...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2009.0167

    authors: Passaes CP,Guimarães ML,Bello G,Morgado MG

    更新日期:2009-12-01 00:00:00

  • Identification of MIP-1 alpha/LD78 as a monocyte chemoattractant released by the HTLV-I-transformed cell line MT4.

    abstract::It is known that the HTLV-I-transformed cell line MT4 releases chemotactic activity for monocytes spontaneously. The MT4 monocyte chemoattractant was purified to homogeneity and sequencing of 25 amino acids revealed identity with the C-C chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha/LD78). An anti-MIP...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1995.11.155

    authors: Bertini R,Luini W,Sozzani S,Bottazzi B,Ruggiero P,Boraschi D,Saggioro D,Chieco-Bianchi L,Proost P,van Damme J

    更新日期:1995-01-01 00:00:00

  • Predominance of three NF-kappaB binding sites in the long terminal repeat region of HIV Type 1 subtype C isolates from Zambia.

    abstract::Human immunodeficiency virus type-1 (HIV-1) is a leading cause of mortality and morbidity in the world, with almost 46 million people infected globally. HIV-1 subtype C accounts for 55% of these infections. In Zambia, the majority of HIV-1 infections are subtype C. However, to its north most countries have non-subtype...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2005.21.901

    authors: Munkanta M,Handema R,Kasai H,Gondwe C,Deng X,Yamashita A,Asagi T,Yamamoto N,Ito M,Kasolo F,Terunuma H

    更新日期:2005-10-01 00:00:00

  • Sequence specificity of the human immunodeficiency virus type 2 (hiv-2) long terminal repeat u3 region in vivo allows subtyping of the principal hiv-2 viral subtypes a and b.

    abstract::Sequences from the nef/LTR overlap region of the human immunodeficiency virus type 2 (HIV-2) genome were amplified from uncultured peripheral blood mononuclear cells (PBMCs) from 40 HIV-2-infected individuals in The Gambia, West Africa. Additional sequences from the plasma of three blood donors were also derived. Anal...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201750063197

    authors: Berry N,Ariyoshi K,Balfe P,Tedder R,Whittle H

    更新日期:2001-02-10 00:00:00