Aggregate complexes of HIV-1 induced by multimeric antibodies

Retrovirology

Robin J Shattock²  Georgia D Tomaras⁴  Thomas N Denny⁴  Jerome H Kim³  Merlin L Robb³  Nelson L Michael³  Supachai Rerks-Ngarm⁷  Sorachai Nitayaphan⁸  Jaranit Kaewkungwal⁶  Punnee Pitisuttithum⁶  Barton Haynes⁴  David C Montefiori⁴  Guido Ferrari⁴  Kwan Ki Hwang⁴  Xiaoying Shen⁴  Pinghuang Liu⁵  Katja Klein²  Deborah F King²  Daniel J Stieh¹ 

[1] Current address: Department of Cellular and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago 60611, IL, USA;Mucosal Infection & Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary¿s Campus, London W2 1PG, UK;Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America;Duke Human Vaccine Center, Duke University Medical Center, Durham 27710, NC, USA;Current address: Division of Swine Infectious Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China;Faculty of Tropical Medicine, Mahidol, Thailand;Ministry of Public Health, Bangkok, Thailand;Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

关键词: Aggregation;    Immunoglobulin A;    Mucosal immunity;    HIV-1;   

Others  :  1152287
DOI  :  10.1186/s12977-014-0078-8

 received in 2014-03-04, accepted in 2014-08-30,  发布年份 2014

【 摘 要 】

Background

Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry.

Results

The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA.

Conclusions

These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

【 授权许可】

   
2014 Stieh et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Burton DR, Desrosiers RC, Doms RW, Koff WC, Kwong PD, Moore JP, Nabel GJ, Sodroski J, Wilson IA, Wyatt RT: HIV vaccine design and the neutralizing antibody problem. Nat Immunol 2004, 5(3):233-236.
• [2]Kwong PD, Mascola JR, Nabel GJ: Rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1. Cold Spring Harb Perspect Med 2011, 1(1):a007278.
• [3]Shattock RJ, Haynes BF, Pulendran B, Flores J, Esparza J: Improving defences at the portal of HIV entry: mucosal and innate immunity. PLoS Med 2008, 5(4):e81.
• [4]Kraehenbuhl JP, Neutra MR: Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 1992, 72(4):853-879.
• [5]Mantis NJ, Rol N, Corthesy B: Secretory IgA¿s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 2011, 4(6):603-611.
• [6]Czerkinsky C, Prince SJ, Michalek SM, Jackson S, Russell MW, Moldoveanu Z, McGhee JR, Mestecky J: IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans. Proc Natl Acad Sci U S A 1987, 84(8):2449-2453.
• [7]Brandtzaeg P: Molecular and cellular aspects of the secretory immunoglobulin system. APMIS 1995, 103(1):1-19.
• [8]Strugnell RA, Wijburg OLC: The role of secretory antibodies in infection immunity. Nat Rev Micro 2010, 8(9):656-667.
• [9]Kutteh WH, Prince SJ, Hammond KR, Kutteh CC, Mestecky J: Variations in immunoglobulins and IgA subclasses of human uterine cervical secretions around the time of ovulation. Clin Exp Immunol 1996, 104(3):538-542.
• [10]Mestecky J, Russell MW: IgA subclasses. Monogr Allergy 1986, 19:277-301.
• [11]Hope TJ: Moving ahead an HIV vaccine: to neutralize or not, a key HIV vaccine question. Nat Med 2011, 17(10):1195-1197.
• [12]Shattock RJ, Moore JP: Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 2003, 1(1):25-34.
• [13]Tomaras GD, Haynes BF: Strategies for eliciting HIV-1 inhibitory antibodies. Curr Opin HIV AIDS 2010, 5(5):421-427.
• [14]Che Z, Olson NH, Leippe D, Lee WM, Mosser AG, Rueckert RR, Baker TS, Smith TJ: Antibody-mediated neutralization of human rhinovirus 14 explored by means of cryoelectron microscopy and X-ray crystallography of virus-Fab complexes. J Virol 1998, 72(6):4610-4622.
• [15]Colonno RJ, Callahan PL, Leippe DM, Rueckert RR, Tomassini JE: Inhibition of rhinovirus attachment by neutralizing monoclonal antibodies and their Fab fragments. J Virol 1989, 63(1):36-42.
• [16]Brioen P, Dekegel D, Boeye A: Neutralization of poliovirus by antibody-mediated polymerization. Virology 1983, 127(2):463-468.
• [17]Semler BL, Ehrenfeld E: Molecular Aspects Of Picornavirus Infection And Detection. In Washington, D.C.: American Society for Microbiology; 1989.
• [18]Hassan PA, Rana S, Verma G: Making sense of brownian motion: colloid characterization by dynamic light scattering.Langmuir 2014, Epub.
• [19]Lewis DJ, Fraser CA, Mahmoud AN, Wiggins RC, Woodrow M, Cope A, Cai C, Giemza R, Jeffs SA, Manoussaka M, Cole T, Cranage MP, Shattock RJ, Lacey CJ: Phase I randomised clinical trial of an HIV-1(CN54), clade C, trimeric envelope vaccine candidate delivered vaginally. PLoS One 2011, 6(9):e25165.
• [20]Stieh DJ, Phillips JL, Rogers PM, King DF, Cianci GC, Jeffs SA, Gnanakaran S, Shattock RJ: Dynamic electrophoretic fingerprinting of the HIV-1 envelope glycoprotein. Retrovirology 2013, 10:33. BioMed Central Full Text
• [21]Chertova E, Chertov O, Coren LV, Roser JD, Trubey CM, Bess JW Jr, Sowder RC 2nd, Barsov E, Hood BL, Fisher RJ, Nagashima K, Conrads TP, Veenstra TD, Lifson JD, Ott DE: Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages. J Virol 2006, 80(18):9039-9052.
• [22]Rossio JL, Esser MT, Suryanarayana K, Schneider DK, Bess JW Jr, Vasquez GM, Wiltrout TA, Chertova E, Grimes MK, Sattentau Q, Arthur LO, Henderson LE, Lifson JD: Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol 1998, 72(10):7992-8001.
• [23]White TA, Bartesaghi A, Borgnia MJ, Meyerson JR, de la Cruz MJ, Bess JW, Nandwani R, Hoxie JA, Lifson JD, Milne JL, Subramaniam S: Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure. PLoS Pathog 2010, 6(12):e1001249.
• [24]Trubey CM, Chertova E, Coren LV, Hilburn JM, Hixson CV, Nagashima K, Lifson JD, Ott DE: Quantitation of HLA class II protein incorporated into human immunodeficiency type 1 virions purified by anti-CD45 immunoaffinity depletion of microvesicles. J Virol 2003, 77(23):12699-12709.
• [25]Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009, 361(23):2209-2220.
• [26]Salmon-Ceron D, Excler JL, Finkielsztejn L, Autran B, Gluckman JC, Sicard D, Matthews TJ, Meignier B, Valentin C, El Habib R, Blondeau C, Raux M, Moog C, Tartaglia J, Chong P, Klein M, Milcamps B, Heshmati F, Plotkin S: Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida. AIDS Res Hum Retroviruses 1999, 15(7):633-645.
• [27]Montefiori DC, Karnasuta C, Huang Y, Ahmed H, Gilbert P, de Souza MS, McLinden R, Tovanabutra S, Laurence-Chenine A, Sanders-Buell E, Moody MA, Bonsignori M, Ochsenbauer C, Kappes J, Tang H, Greene K, Gao H, LaBranche CC, Andrews C, Polonis VR, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Self SG, Berman PW, Francis D, Sinangil F, Lee C, Tartaglia J, et al.: Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J Infect Dis 2012, 206(3):431-441.
• [28]Tomaras GD, Ferrari G, Shen X, Alam SM, Liao HX, Pollara J, Bonsignori M, Moody MA, Fong Y, Chen X, Poling B, Nicholson CO, Zhang R, Lu X, Parks R, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Gilbert PB, Kim JH, Michael NL, Montefiori DC, Haynes BF: Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proc Natl Acad Sci U S A 2013, 110(22):9019-9024.
• [29]Liu P, Yates NL, Shen X, Bonsignori M, Moody MA, Liao HX, Fong Y, Alam SM, Overman RG, Denny T, Ferrari G, Ochsenbauer C, Kappes JC, Polonis VR, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Montefiori DC, Gilbert P, Michael NL, Kim JH, Haynes BF, Tomaras GD: Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees. J Virol 2013, 87(14):7828-7836.
• [30]Kerr MA: The structure and function of human IgA. Biochem J 1990, 271(2):285-296.
• [31]Karasavvas N, Billings E, Rao M, Williams C, Zolla-Pazner S, Bailer RT, Koup RA, Madnote S, Arworn D, Shen X, Tomaras GD, Currier JR, Jiang M, Magaret C, Andrews C, Gottardo R, Gilbert P, Cardozo TJ, Rerks-Ngarm S, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Paris R, Greene K, Gao H, Gurunathan S, Tartaglia J, Sinangil F, Korber BT, Montefiori DC, et al.: The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120. AIDS Res Hum Retroviruses 2012, 28(11):1444-1457.
• [32]Bonsignori M1, Pollara J, Moody MA, Alpert MD, Chen X, Hwang KK, Gilbert PB, Huang Y, Gurley TC, Kozink DM, Marshall DJ, Whitesides JF, Tsao CY, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Kim JH, Michael NL, Tomaras GD, Montefiori DC, Lewis GK, DeVico A, Evans DT, Ferrari G, Liao HX, Haynes BF: Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol 2012, 86(21):11521-11532.
• [33]Klein JS, Bjorkman PJ: Few and far between: how HIV may be evading antibody avidity. PLoS Pathog 2010, 6(5):e1000908.
• [34]Mouquet H1, Scheid JF, Zoller MJ, Krogsgaard M, Ott RG, Shukair S, Artyomov MN, Pietzsch J, Connors M, Pereyra F, Walker BD, Ho DD, Wilson PC, Seaman MS, Eisen HN, Chakraborty AK, Hope TJ, Ravetch JV, Wardemann H, Nussenzweig MC: Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. Nature 2010, 467(7315):591-595.
• [35]Thomas AA, Vrijsen R, Boeye A: Relationship between poliovirus neutralization and aggregation. J Virol 1986, 59(2):479-485.
• [36]Bonner A, Furtado PB, Almogren A, Kerr MA, Perkins SJ: Implications of the near-planar solution structure of human myeloma dimeric IgA1 for mucosal immunity and IgA nephropathy. J Immunol 2008, 180(2):1008-1018.
• [37]Matyas GR, Beck Z, Karasavvas N, Alving CR: Lipid binding properties of 4E10, 2 F5, and WR304 monoclonal antibodies that neutralize HIV-1. Biochim Biophys Acta 2009, 1788(3):660-665.
• [38]Chakrabarti BK, Walker LM, Guenaga JF, Ghobbeh A, Poignard P, Burton DR, Wyatt RT: Direct antibody access to the HIV-1 membrane-proximal external region positively correlates with neutralization sensitivity. J Virol 2011, 85(16):8217-8226.
• [39]Alam SM, Morelli M, Dennison SM, Liao HX, Zhang R, Xia SM, Rits-Volloch S, Sun L, Harrison SC, Haynes BF, Chen B: Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci U S A 2009, 106(48):20234-20239.
• [40]Muranyi W, Malkusch S, Muller B, Heilemann M, Krausslich HG: Super-resolution microscopy reveals specific recruitment of HIV-1 envelope proteins to viral assembly sites dependent on the envelope C-terminal tail. PLoS Pathog 2013, 9(2):e1003198.
• [41]Alam SM, Liao HX, Tomaras GD, Bonsignori M, Tsao CY, Hwang KK, Chen H, Lloyd KE, Bowman C, Sutherland L, Jeffries TL Jr, Kozink DM, Stewart S, Anasti K, Jaeger FH, Parks R, Yates NL, Overman RG, Sinangil F, Berman PW, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Karasavva N, Rerks-Ngarm S, Kim JH, Michael NL, Zolla-Pazner S, Santra S, Letvin NL, et al.: Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion. J Virol 2013, 87(3):1554-1568.
• [42]Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, et al.: Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 2012, 366(14):1275-1286.
• [43]Watkins JD, Sholukh AM, Mukhtar MM, Siddappa NB, Lakhashe SK, Kim M, Reinherz EL, Gupta S, Forthal DN, Sattentau QJ, Villinger F, Corti D, Ruprecht RM: Anti-HIV IgA isotypes: differential virion capture and inhibition of transcytosis are linked to prevention of mucosal R5 SHIV transmission. AIDS 2013, 27(9):F13-F20.
• [44]Greenhead P, Hayes P, Watts PS, Laing KG, Griffin GE, Shattock RJ: Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 2000, 74(12):5577-5586.
• [45]Arthur LO, Bess JW Jr, Chertova EN, Rossio JL, Esser MT, Benveniste RE, Henderson LE, Lifson JD: Chemical inactivation of retroviral infectivity by targeting nucleocapsid protein zinc fingers: a candidate SIV vaccine. AIDS Res Hum Retroviruses 1998, 14(Suppl 3):S311-S319.
• [46]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 HX, Self SG, Landucci G, Forthal DN, Weinhold KJ, Keele BF, Hahn BH, Greenberg ML, Morris L, Karim SS, 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(24):12449-12463.