Top

Published in:

Open Access 01-12-2013 | Research

Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models

Authors: Miguel Lacerda, Penny L Moore, Nobubelo K Ngandu, Michael Seaman, Elin S Gray, Ben Murrell, Mohan Krishnamoorthy, Molati Nonyane, Maphuti Madiga, Constantinos Kurt Wibmer, Daniel Sheward, Robert T Bailer, Hongmei Gao, Kelli M Greene, Salim S Abdool Karim, John R Mascola, Bette TM Korber, David C Montefiori, Lynn Morris, Carolyn Williamson, Cathal Seoighe, the CAVD-NSDP Consortium

Published in: Virology Journal | Issue 1/2013

Abstract

Background

Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine.

Methods

We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope.

Results

We applied our method to ID₅₀ neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF) > 6), a subset of which were experimentally confirmed using site-directed mutagenesis.

Conclusions

Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.

Available only for authorised users

Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, Chavez LL, Decamp AC, Parks RJ, Ashley VC, Lucas JT, Cohen M, Eron J, Hicks CB, Liao H-X, Self SG, Landucci G, Forthal DN, Weinhold KJ, Keele BF, Hahn BH, Greenberg ML, Morris L, Karim SSA, Blattner WA, Montefiori DC, Shaw GM, Perelson AS, Haynes BF: Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J Virol. 2008, 82: 12449-12463. 10.1128/JVI.01708-08.PubMedPubMedCentralCrossRef

Tomaras GD, Haynes BF: HIV-1-specific antibody responses during acute and chronic HIV-1 infection. Curr Opin HIV AIDS. 2009, 4: 373-379. 10.1097/COH.0b013e32832f00c0.PubMedPubMedCentralCrossRef

McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF: The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol. 2010, 10: 11-23. 10.1038/nri2674.PubMedPubMedCentralCrossRef

Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM: Antibody neutralization and escape by HIV-1. Nature. 2003, 422: 307-312. 10.1038/nature01470.PubMedCrossRef

Richman DD, Wrin T, Little SJ, Petropoulos CJ: Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci USA. 2003, 100: 4144-4149. 10.1073/pnas.0630530100.PubMedPubMedCentralCrossRef

Li B, Decker JM, Johnson RW, Bibollet-Ruche F, Wei X, Mulenga J, Allen S, Hunter E, Hahn BH, Shaw GM, Blackwell JL, Derdeyn CA: Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1. J Virol. 2006, 80: 5211-5218. 10.1128/JVI.00201-06.PubMedPubMedCentralCrossRef

Gray ES, Moore PL, Choge IA, Decker JM, Bibollet-Ruche F, Li H, Leseka N, Treurnicht F, Mlisana K, Shaw GM, Karim SSA, Williamson C, Morris L: Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection. J Virol. 2007, 81: 6187-6196. 10.1128/JVI.00239-07.PubMedPubMedCentralCrossRef

Frost SDW, Wrin T, Smith DM, Kosakovsky Pond SL, Liu Y, Paxinos E, Chappey C, Galovich J, Beauchaine J, Petropoulos CJ, Little SJ, Richman DD: Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection. Proc Natl Acad Sci USA. 2005, 102: 18514-18519. 10.1073/pnas.0504658102.PubMedPubMedCentralCrossRef

Rong R, Li B, Lynch RM, Haaland RE, Murphy MK, Mulenga J, Allen SA, Pinter A, Shaw GM, Hunter E, Robinson JE, Gnanakaran S, Derdeyn CA: Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways. PLoS Pathog. 2009, 5: e1000594-10.1371/journal.ppat.1000594.PubMedPubMedCentralCrossRef

10.

Doria-Rose NA, Klein RM, Manion MM, O’Dell S, Phogat A, Chakrabarti B, Hallahan CW, Migueles SA, Wrammert J, Ahmed R, Nason M, Wyatt RT, Mascola JR, Connors M: Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol. 2009, 83: 188-199. 10.1128/JVI.01583-08.PubMedPubMedCentralCrossRef

11.

Sather DN, Armann J, Ching LK, Mavrantoni A, Sellhorn G, Caldwell Z, Yu X, Wood B, Self S, Kalams S, Stamatatos L: Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol. 2009, 83: 757-769. 10.1128/JVI.02036-08.PubMedPubMedCentralCrossRef

12.

Gray ES, Madiga MC, Hermanus T, Moore PL, Wibmer CK, Tumba NL, Werner L, Mlisana K, Sibeko S, Williamson C, Abdool Karim SS, Morris L: The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J Virol. 2011, 85: 4828-4840. 10.1128/JVI.00198-11.PubMedPubMedCentralCrossRef

13.

Stamatatos L, Morris L, Burton DR, Mascola JR: Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?. Nat Med. 2009, 15: 866-870.PubMed

14.

Euler Z, van Gils MJ, Bunnik EM, Phung P, Schweighardt B, Wrin T, Schuitemaker H: Cross-reactive neutralizing humoral immunity does not protect from HIV type 1 disease progression. J Infect Dis. 2010, 201: 1045-1053. 10.1086/651144.PubMedCrossRef

15.

Gnanakaran S, Daniels MG, Bhattacharya T, Lapedes AS, Sethi A, Li M, Tang H, Greene K, Gao H, Haynes BF, Cohen MS, Shaw GM, Seaman MS, Kumar A, Gao F, Montefiori DC, Korber B: Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies. PLoS Comput Biol. 2010, 6: e1000955-10.1371/journal.pcbi.1000955.PubMedPubMedCentralCrossRef

16.

Kwong PD, Doyle ML, Casper DJ, Cicala C, Leavitt SA, Majeed S, Steenbeke TD, Venturi M, Chaiken I, Fung M, Katinger H, Parren PWIH, Robinson J, Van Ryk D, Wang L, Burton DR, Freire E, Wyatt R, Sodroski J, Hendrickson WA, Arthos J: HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature. 2002, 420: 678-682. 10.1038/nature01188.PubMedCrossRef

17.

Mahalanabis M, Jayaraman P, Miura T, Pereyra F, Chester EM, Richardson B, Walker B, Haigwood NL: Continuous viral escape and selection by autologous neutralizing antibodies in drug-naive human immunodeficiency virus controllers. J Virol. 2009, 83: 662-672. 10.1128/JVI.01328-08.PubMedPubMedCentralCrossRef

18.

Deeks SG, Schweighardt B, Wrin T, Galovich J, Hoh R, Sinclair E, Hunt P, McCune JM, Martin JN, Petropoulos CJ, Hecht FM: 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. J Virol. 2006, 80: 6155-6164. 10.1128/JVI.00093-06.PubMedPubMedCentralCrossRef

19.

Walker LM, Phogat SK, Chan-Hui P-Y, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DR: Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009, 326: 285-289. 10.1126/science.1178746.PubMedPubMedCentralCrossRef

20.

Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien J-P, Wang S-K, Ramos A, Chan-Hui P-Y, Moyle M, Mitcham JL, Hammond PW, Olsen OA, Phung P, Fling S, Wong C-H, Phogat S, Wrin T, Simek MD, Principal Investigators PG, Koff WC, Wilson IA, Burton DR, Poignard P: Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011, 477: 466-470. 10.1038/nature10373.PubMedPubMedCentralCrossRef

21.

Wu X, Yang Z-Y, Li Y, Hogerkorp C-M, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O’Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR: Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010, 329: 856-861. 10.1126/science.1187659.PubMedPubMedCentralCrossRef

22.

Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK, Alam SM, Wang T, Yang Y, Zhang B, Migueles SA, Wyatt R, Haynes BF, Kwong PD, Mascola JR, Connors M: Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012, 491: 406-412. 10.1038/nature11544.PubMedCrossRef

23.

Burton DR, Pyati J, Koduri R, Sharp SJ, Thornton GB, Parren PW, Sawyer LS, Hendry RM, Dunlop N, Nara PL: Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994, 266: 1024-1027. 10.1126/science.7973652.PubMedCrossRef

24.

Pejchal R, Gach JS, Brunel FM, Cardoso RM, Stanfield RL, Dawson PE, Burton DR, Zwick MB, Wilson IA: A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies. J Virol. 2009, 83: 8451-8462. 10.1128/JVI.00685-09.PubMedPubMedCentralCrossRef

25.

Sanders RW, Venturi M, Schiffner L, Kalyanaraman R, Katinger H, Lloyd KO, Kwong PD, Moore JP: The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol. 2002, 76: 7293-7305. 10.1128/JVI.76.14.7293-7305.2002.PubMedPubMedCentralCrossRef

26.

Scanlan CN, Pantophlet R, Wormald MR, Ollmann Saphire E, Stanfield R, Wilson IA, Katinger H, Dwek RA, Rudd PM, Burton DR: The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120. J Virol. 2002, 76: 7306-7321. 10.1128/JVI.76.14.7306-7321.2002.PubMedPubMedCentralCrossRef

27.

Zwick MB, Labrijn AF, Wang M, Spenlehauer C, Saphire EO, Binley JM, Moore JP, Stiegler G, Katinger H, Burton DR, Parren PWHI: Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol. 2001, 75: 10892-10905. 10.1128/JVI.75.22.10892-10905.2001.PubMedPubMedCentralCrossRef

28.

Mascola JR, Montefiori DC: The role of antibodies in HIV vaccines. Annu Rev Immunol. 2010, 28: 413-444. 10.1146/annurev-immunol-030409-101256.PubMedCrossRef

29.

Tomaras GD, Binley JM, Gray ES, Crooks ET, Osawa K, Moore PL, Tumba N, Tong T, Shen X, Yates NL, Decker J, Wibmer CK, Gao F, Alam SM, Easterbrook P, Abdool Karim S, Kamanga G, Crump JA, Cohen M, Shaw GM, Mascola JR, Haynes BF, Montefiori DC, Morris L: Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals. J Virol. 2011, 85: 11502-11519. 10.1128/JVI.05363-11.PubMedPubMedCentralCrossRef

30.

EL-Manzalawy Y, Honavar V: Recent advances in B-cell epitope prediction methods. Immunome Research. 2010, 6: S2-PubMedPubMedCentralCrossRef

31.

Greenbaum JA, Andersen PH, Blythe M, Bui H-H, Cachau RE, Crowe J, Davies M, Kolaskar AS, Lund O, Morrison S, Mumey B, Ofran Y, Pellequer J-L, Pinilla C, Ponomarenko JV, Raghava GPS, van Regenmortel MHV, Roggen EL, Sette A, Schlessinger A, Sollner J, Zand M, Peters B: Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools. J Mol Recognit. 2007, 20: 75-82. 10.1002/jmr.815.PubMedCrossRef

32.

Sweredoski MJ, Baldi P: PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure. Bioinformatics. 2008, 24: 1459-60. 10.1093/bioinformatics/btn199.PubMedCrossRef

33.

Georgiev IS, Doria-Rose NA, Zhou T, Kwon YD, Staupe RP, Moquin S, Chuang G-Y, Louder MK, Schmidt SD, Altae-Tran HR, Bailer RT, McKee K, Nason M, O’Dell S, Ofek G, Pancera M, Srivatsan S, Shapiro L, Connors M, Migueles SA, Morris L, Nishimura Y, Martin MA, Mascola JR, Kwong PD: Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science. 2013, 340: 751-756. 10.1126/science.1233989.PubMedCrossRef

34.

Moore PL, Gray ES, Sheward D, Madiga M, Ranchobe N, Lai Z, Honnen WJ, Nonyane M, Tumba N, Hermanus T, Sibeko S, Mlisana K, Abdool Karim SS, Williamson C, Pinter A, Morris L: Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J Virol. 2011, 85: 3128-3141. 10.1128/JVI.02658-10.PubMedPubMedCentralCrossRef

35.

Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, Hermanus T, Bajimaya S, Tumba NL, Abrahams M-R, Lambson BE, Ranchobe N, Ping L, Ngandu N, Abdool Karim Q, Abdool Karim SS, Swanstrom RI, Seaman MS, Williamson C, Morris L: Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. Nat Med. 2012, 18: 1688-1692. 10.1038/nm.2985.PubMedPubMedCentralCrossRef

36.

Blish CA, Nguyen M-A, Overbaugh J: Enhancing exposure of HIV-1 neutralization epitopes through mutations in gp41. PLoS Med. 2008, 5: e9-10.1371/journal.pmed.0050009.PubMedPubMedCentralCrossRef

37.

Lovelace E, Xu H, Blish CA, Strong R, Overbaugh J: The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Virology. 2011, 421: 235-244. 10.1016/j.virol.2011.09.032.PubMedPubMedCentralCrossRef

38.

Poon AFY, Lewis FI, Pond SLK, Frost SDW: An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope. PLoS Comput Biol. 2007, 3: e231-10.1371/journal.pcbi.0030231.PubMedPubMedCentralCrossRef

39.

Gray ES, Madiga MC, Moore PL, Mlisana K, Abdool Karim SS, Binley JM, Shaw GM, Mascola JR, Morris L: Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region. J Virol. 2009, 83: 11265-11274. 10.1128/JVI.01359-09.PubMedPubMedCentralCrossRef

40.

Tang H, Robinson JE, Gnanakaran S, Li M, Rosenberg ES, Perez LG, Haynes BF, Liao H-X, LaBranche CC, Korber BT, Montefiori DC: Epitopes immediately below the base of the V3 loop of gp120 as targets for the initial autologous neutralizing antibody response in Two HIV-1 subtype B-infected individuals. J Virol. 2011, 85: 9286-9299. 10.1128/JVI.02286-10.PubMedPubMedCentralCrossRef

41.

Morris L, Chen X, Alam M, Tomaras G, Zhang R, Marshall DJ, Chen B, Parks R, Foulger A, Jaeger F, Donathan M, Bilska M, Gray ES, Abdool Karim SS, Kepler TB, Whitesides J, Montefiori D, Moody MA, Liao H-X, Haynes BF: Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. PLoS One. 2011, 6: e23532-10.1371/journal.pone.0023532.PubMedPubMedCentralCrossRef

42.

Lacerda M, Scheffler K, Seoighe C: Epitope discovery with phylogenetic hidden Markov models. Mol Biol Evol. 2010, 27: 1212-1220. 10.1093/molbev/msq008.PubMedPubMedCentralCrossRef

43.

Bhattacharya T, Daniels M, Heckerman D, Foley B, Frahm N, Kadie C, Carlson J, Yusim K, McMahon B, Gaschen B, Mallal S, Mullins JI, Nickle DC, Herbeck J, Rousseau C, Learn GH, Miura T, Brander C, Walker B, Korber B: Founder effects in the assessment of HIV polymorphisms and HLA allele associations. Science. 2007, 315: 1583-6. 10.1126/science.1131528.PubMedCrossRef

44.

McLellan JS, Pancera M, Carrico C, Gorman J, Julien J-P, Khayat R, Louder R, Pejchal R, Sastry M, Dai K, O’Dell S, Patel N, Shahzad-ul-Hussan S, Yang Y, Zhang B, Zhou T, Zhu J, Boyington JC, Chuang G-Y, Diwanji D, Georgiev I, Do Kwon Y, Lee D, Louder MK, Moquin S, Schmidt SD, Yang Z-Y, Bonsignori M, Crump JA, Kapiga SH, et al: Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011, 480: 336-343. 10.1038/nature10696.PubMedPubMedCentralCrossRef

45.

Felsenstein J: Phylogenies and the comparative method. Am Nat. 1985, 125: 1-15. 10.1086/284325.CrossRef

46.

Butler MA, King AA: Phylogenetic comparative analysis: a modeling approach for adaptive evolution. Am Nat. 2004, 164: 683-695. 10.1086/426002.CrossRef

47.

Landis MJ, Schraiber JG, Liang M: Phylogenetic analysis using lévy processes: finding jumps in the evolution of continuous traits. Syst Biol. 2013, 62: 193-204. 10.1093/sysbio/sys086.PubMedPubMedCentralCrossRef

48.

Van Loggerenberg F, Mlisana K, Williamson C, Auld SC, Morris L, Gray CM, Abdool Karim Q, Grobler A, Barnabas N, Iriogbe I, Abdool Karim SS: Establishing a cohort at high risk of HIV infection in South Africa: challenges and experiences of the CAPRISA 002 acute infection study. PLoS One. 2008, 3: e1954-10.1371/journal.pone.0001954.PubMedPubMedCentralCrossRef

49.

Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SDW: GARD: a genetic algorithm for recombination detection. Bioinformatics. 2006, 22: 3096-3098. 10.1093/bioinformatics/btl474.PubMedCrossRef

50.

Arenas M, Posada D: Coalescent simulation of intracodon recombination. Genetics. 2010, 184: 429-437. 10.1534/genetics.109.109736.PubMedPubMedCentralCrossRef

51.

Guindon S, Gascuel O: A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 2003, 52: 696-704. 10.1080/10635150390235520.PubMedCrossRef

52.

Halpern AL, Bruno WJ: Evolutionary distances for protein-coding sequences: modeling site-specific residue frequencies. Mol Biol Evol. 1998, 15: 910-7. 10.1093/oxfordjournals.molbev.a025995.PubMedCrossRef

53.

Murrell B, de Oliveira T, Seebregts C, Kosakovsky Pond SL, Scheffler K, on behalf of the Southern African Treatment and Resistance Network (SATuRN) Consortium: Modeling HIV-1 drug resistance as episodic directional selection. PLoS Comput Biol. 2012, 8: e1002507-10.1371/journal.pcbi.1002507.PubMedPubMedCentralCrossRef

54.

Kosakovsky Pond SL, Frost SDW, Muse SV: HyPhy: hypothesis testing using phylogenies. Bioinformatics. 2005, 21: 676-9. 10.1093/bioinformatics/bti079.CrossRef

55.

Kass RE, Raftery AE: Bayes factors. J Am Stat Assoc. 1995, 90: 773-795. 10.1080/01621459.1995.10476572.CrossRef

56.

Efron B: Size, power and false discovery rates. Ann Statist. 2007, 35: 1351-1377. 10.1214/009053606000001460.CrossRef

57.

Gilks WR, Richardson S, Spiegelhalter DJ: Introducing Markov chain Monte Carlo. Markov Chain Monte Carlo in Practice. Edited by: Gilks WR, Richardson S, Spiegelhalter DJ. 1996, United States of America: Chapman and Hall/CRC, 1-19.

Title: Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models
Authors: Miguel Lacerda
Penny L Moore
Nobubelo K Ngandu
Michael Seaman
Elin S Gray
Ben Murrell
Mohan Krishnamoorthy
Molati Nonyane
Maphuti Madiga
Constantinos Kurt Wibmer
Daniel Sheward
Robert T Bailer
Hongmei Gao
Kelli M Greene
Salim S Abdool Karim
John R Mascola
Bette TM Korber
David C Montefiori
Lynn Morris
Carolyn Williamson
Cathal Seoighe
the CAVD-NSDP Consortium
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/1743-422X-10-347

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer

Evolution of a reassortant North American gull influenza virus lineage: drift, shift and stability

Detection of hepatitis C virus (HCV) negative strand RNA and NS3 protein in peripheral blood mononuclear cells (PBMC): CD3+, CD14+ and CD19+

A neutralization assay for respiratory syncytial virus using a quantitative PCR-based endpoint assessment

Inactivation of the novel avian influenza A (H7N9) virus under physical conditions or chemical agents treatment

A duplex, SYBR Green I-based RT-qPCR assay for the simultaneous detection of Apple chlorotic leaf spot virus and Cherry green ring mottle virus in peach

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials