For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
42
views
21
references
 Top references
cited by
124
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      81
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.

      Author(s): 1 , 1 , 2 , 3 , 4 , 1 , 1 , 5 , 6 , 7 , 1 , 1 , 5 , 1 , 3 , 4 , 3 , 1 , 1 , 2 , 3 , 4 , 8 , 3 , 3 , 1 , 1 , 9 , 10 , 6 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 12 , 8 , 5 , 3 , 4 , 1 , 1 , 18 , 2 , 3 , 4
      Publication date (Electronic):
      Journal: Nature medicine
      Publisher: Springer Nature

      Read this article at

      ScienceOpenPublisherPubMed
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.

          Related collections

          Most cited references21

          • Record: found
          • Abstract: found
          • Article: not found

          Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys

          Dan Barouch, James B. Whitney, Brian Moldt … (2013)
          HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans.
          Article 0 comments Cited 251 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing.

            Jesus Salazar-Gonzalez, Elizabeth Bailes, Kimmy Pham … (2008)
            Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. Here we describe an experimental approach to analyze HIV-1 env genes as intact genetic units amplified from plasma virion RNA by single-genome amplification (SGA), followed by direct sequencing of uncloned DNA amplicons. We show that this strategy precludes in vitro artifacts caused by Taq-induced nucleotide substitutions and template switching, provides an accurate representation of the env quasispecies in vivo, and has an overall error rate (including nucleotide misincorporation, insertion, and deletion) of less than 8 x 10(-5). Applying this method to the analysis of virus in plasma from 12 Zambian subjects from whom samples were obtained within 3 months of seroconversion, we show that transmitted or early founder viruses can be identified and that molecular pathways and rates of early env diversification can be defined. Specifically, we show that 8 of the 12 subjects were each infected by a single virus, while 4 others acquired more than one virus; that the rate of virus evolution in one subject during an 80-day period spanning seroconversion was 1.7 x 10(-5) substitutions per site per day; and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. We also compared the results of the SGA approach with those of more-conventional bulk PCR amplification methods performed on the same patient samples and found that the latter is associated with excessive rates of Taq-induced recombination, nucleotide misincorporation, template resampling, and cloning bias. These findings indicate that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately.
            Article 0 comments Cited 243 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Clinical pharmacokinetics of therapeutic monoclonal antibodies.

              Ron J. Keizer, Alwin D. R. Huitema, Jan Schellens … (2010)
              Monoclonal antibodies (mAbs) have been used in the treatment of various diseases for over 20 years and combine high specificity with generally low toxicity. Their pharmacokinetic properties differ markedly from those of non-antibody-type drugs, and these properties can have important clinical implications. mAbs are administered intravenously, intramuscularly or subcutaneously. Oral administration is precluded by the molecular size, hydrophilicity and gastric degradation of mAbs. Distribution into tissue is slow because of the molecular size of mAbs, and volumes of distribution are generally low. mAbs are metabolized to peptides and amino acids in several tissues, by circulating phagocytic cells or by their target antigen-containing cells. Antibodies and endogenous immunoglobulins are protected from degradation by binding to protective receptors (the neonatal Fc-receptor [FcRn]), which explains their long elimination half-lives (up to 4 weeks). Population pharmacokinetic analyses have been applied in assessing covariates in the disposition of mAbs. Both linear and nonlinear elimination have been reported for mAbs, which is probably caused by target-mediated disposition. Possible factors influencing elimination of mAbs include the amount of the target antigen, immune reactions to the antibody and patient demographics. Bodyweight and/or body surface area are generally related to clearance of mAbs, but clinical relevance is often low. Metabolic drug-drug interactions are rare for mAbs. Exposure-response relationships have been described for some mAbs. In conclusion, the parenteral administration, slow tissue distribution and long elimination half-life are the most pronounced clinical pharmacokinetic characteristics of mAbs.
              Article 0 comments Cited 239 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (iso-abbrev): Nat. Med.
                Title: Nature medicine
                Publisher: Springer Nature
                ISSN (Electronic): 1546-170X
                ISSN (Print): 1078-8956
                Publication date (Electronic): Feb 2017
                Volume: 23
                Issue: 2
                Affiliations
                [1 ] Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
                [2 ] Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
                [3 ] Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
                [4 ] German Center for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
                [5 ] Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
                [6 ] Department of Medicine, University of California, San Diego, San Diego, California, USA.
                [7 ] Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
                [8 ] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
                [9 ] Department of Biomedical Informatics, University of California, San Diego, San Diego, California, USA.
                [10 ] Bioinformatics and System Biology, University of California, San Diego, San Diego, California, USA.
                [11 ] Department of Ophthalmology, Weill Cornell Medical College of Cornell University, New York, New York, USA.
                [12 ] Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
                [13 ] Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.
                [14 ] Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
                [15 ] Einstein/Rockefeller/CUNY Center for AIDS Research, Bronx, New York, USA.
                [16 ] Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
                [17 ] Celldex Therapeutics, Hampton, New Jersey, USA.
                [18 ] Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.
                Article
                Publisher Item ID: nm.4268
                DOI: 10.1038/nm.4268
                PubMed ID: 28092665
                SO-VID: 774af77e-2014-40cc-8894-49a9b86d7dd0
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content81

                See all similar

                Cited by222

                See all cited by

                Most referenced authors2,318

                See all reference authors