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Open Access 01-12-2015 | Research article

Identifiable biomarker and treatment development using HIV-1 long term non-progressor sera

Published in: BMC Immunology | Issue 1/2015

Abstract

Background

HIV-infected long-term non-progressor (LTNP) subjects can prevent viral replication and may harbor useful information for the development of both antibody and active vaccination treatments. In this study we used LTNP sera to examine the epitopes presented to the gp160 protein, and from this procedure we hope to elucidate potential biomarkers pertaining to the level of resistance a patient may have in developing AIDS after infection with HIV. We used five clinical sera samples from LTNP patients to identify common epitopes by ELISA; peptides with high binding to sera were selected and analyzed for conservation among HIV clades. Antibodies were generated against one identified epitope using a chimeric peptide in BALB/c mice, and both the sera from these mice and LTNP sera were tested for viral inhibition capabilities.

Results

A monoclonal antibody, CL3, against one identified epitope was used to compare these epitopes neutralizing capability. LTNP sera was also studied to determine chemokine/cytokine changes in these patients. The sera from LTNP patients 2, 3, 4, and 5 were identified as having the highest titers, and also significantly inhibited syncytia formation in vitro. Finally, the protein cytokine array demonstrated that I-309 and IGFBP-1 decreased in LTNPs, but levels of TIMP-1 and NAP-2 increased significantly.

Conclusions

Our results indicate that the use of LTNP samples may be a useful for identifying further anti-viral epitopes, and may be a possible predictor for determining if patients show higher resistances of converting the HIV infection to AIDS.

Penaloza-MacMaster P, Masopust D, Ahmed R. T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction. Immunology. 2009;128(2):164–71.CrossRefPubMedCentralPubMed

Smalls-Mantey A, Doria-Rose N, Klein R, Patamawenu A, Migueles SA, Ko SY, et al. Antibody-dependent cellular cytotoxicity against primary HIV-infected CD4+ T cells is directly associated with the magnitude of surface IgG binding. J Virol. 2012;86(16):8672–80.CrossRefPubMedCentralPubMed

Beasley RP, Hwang LY, Lin CC, Stevens CE, Wang KY, Sun TS, et al. Hepatitis B immune globulin (HBIG) efficacy in the interruption of perinatal transmission of hepatitis B virus carrier state. Initial report of a randomised double-blind placebo-controlled trial. Lancet. 1981;2(8243):388–93.CrossRefPubMed

Beasley RP, Hwang LY, Stevens CE, Lin CC, Hsieh FJ, Wang KY, et al. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: final report of a randomized double-blind, placebo-controlled trial. Hepatology. 1983;3(2):135–41.CrossRefPubMed

Groothuis JR, Simoes EA, Levin MJ, Hall CB, Long CE, Rodriguez WJ, et al. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group. New England J Med. 1993;329(21):1524–30.CrossRef

Ritz J, Pesando JM, Notis-McConarty J, Clavell LA, Sallan SE, Schlossman SF. Use of monoclonal antibodies as diagnostic and therapeutic reagents in acute lymphoblastic leukemia. Cancer Res. 1981;41(11 Pt 2):4771–5.PubMed

Ma JK, Smith R, Lehner T. Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans. Infect Immun. 1987;55(5):1274–8.PubMedCentralPubMed

Emini EA, Schleif WA, Nunberg JH, Conley AJ, Eda Y, Tokiyoshi S, et al. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992;355(6362):728–30.CrossRefPubMed

Gauduin MC, Safrit JT, Weir R, Fung MS, Koup RA. Pre- and postexposure protection against human immunodeficiency virus type 1 infection mediated by a monoclonal antibody. J Infectious Diseases. 1995;171(5):1203–9.CrossRef

10.

Shibata R, Igarashi T, Haigwood N, Buckler-White A, Ogert R, Ross W, et al. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nat Med. 1999;5(2):204–10.CrossRefPubMed

11.

Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE, et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med. 2000;6(2):207–10.CrossRefPubMed

12.

Baba TW, Liska V, Hofmann-Lehmann R, Vlasak J, Xu W, Ayehunie S, et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med. 2000;6(2):200–6.CrossRefPubMed

13.

Hofmann-Lehmann R, Vlasak J, Rasmussen RA, Smith BA, Baba TW, Liska V, et al. Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge. J Virol. 2001;75(16):7470–80.CrossRefPubMedCentralPubMed

14.

Ferrantelli F, Hofmann-Lehmann R, Rasmussen RA, Wang T, Xu W, Li PL, et al. Post-exposure prophylaxis with human monoclonal antibodies prevented SHIV89.6P infection or disease in neonatal macaques. AIDS. 2003;17(3):301–9.CrossRefPubMed

15.

Gorny MK, Gianakakos V, Sharpe S, Zolla-Pazner S. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc Natl Acad Sci U S A. 1989;86(5):1624–8.CrossRefPubMedCentralPubMed

16.

Tyler DS, Stanley SD, Zolla-Pazner S, Gorny MK, Shadduck PP, Langlois AJ, et al. Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J Immunol. 1990;145(10):3276–82.PubMed

17.

Burton DR, Pyati J, Koduri R, Sharp SJ, Thornton GB, Parren PW, et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994;266(5187):1024–7.CrossRefPubMed

18.

D’Souza MP, Livnat D, Bradac JA, Bridges SH. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J Infectious Diseases. 1997;175(5):1056–62.CrossRef

19.

Roben P, Moore JP, Thali M, Sodroski J, Barbas 3rd CF, Burton DR. Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J Virol. 1994;68(8):4821–8.PubMedCentralPubMed

20.

Scanlan CN, Pantophlet R, Wormald MR, Ollmann Saphire E, Stanfield R, Wilson IA, et al. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1 → 2 mannose residues on the outer face of gp120. J Virol. 2002;76(14):7306–21.CrossRefPubMedCentralPubMed

21.

Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, et al. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol. 1996;70(2):1100–8.PubMedCentralPubMed

22.

Conley AJ, Kessler 2nd JA, Boots LJ, Tung JS, Arnold BA, Keller PM, et al. Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2 F5, an anti-gp41 human monoclonal antibody. Proc Natl Acad Sci U S A. 1994;91(8):3348–52.CrossRefPubMedCentralPubMed

23.

Muster T, Steindl F, Purtscher M, Trkola A, Klima A, Himmler G, et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993;67(11):6642–7.PubMedCentralPubMed

24.

Purtscher M, Trkola A, Gruber G, Buchacher A, Predl R, Steindl F, et al. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retrovir. 1994;10(12):1651–8.CrossRefPubMed

25.

Poignard P, Sabbe R, Picchio GR, Wang M, Gulizia RJ, Katinger H, et al. Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo. Immunity. 1999;10(4):431–8.CrossRefPubMed

26.

Mascola JR, Lewis MG, Stiegler G, Harris D, VanCott TC, Hayes D, et al. Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol. 1999;73(5):4009–18.PubMedCentralPubMed

27.

Li A, Katinger H, Posner MR, Cavacini L, Zolla-Pazner S, Gorny MK, et al. Synergistic neutralization of simian-human immunodeficiency virus SHIV-vpu + by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins. J Virol. 1998;72(4):3235–40.PubMedCentralPubMed

28.

Verrier F, Nadas A, Gorny MK, Zolla-Pazner S. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J Virol. 2001;75(19):9177–86.CrossRefPubMedCentralPubMed

29.

Stiegler G, Armbruster C, Vcelar B, Stoiber H, Kunert R, Michael NL, et al. Antiviral activity of the neutralizing antibodies 2 F5 and 2G12 in asymptomatic HIV-1-infected humans: a phase I evaluation. AIDS. 2002;16(15):2019–25.CrossRefPubMed

30.

Armbruster C, Stiegler GM, Vcelar BA, Jager W, Michael NL, Vetter N, et al. A phase I trial with two human monoclonal antibodies (hMAb 2 F5, 2G12) against HIV-1. AIDS. 2002;16(2):227–33.CrossRefPubMed

31.

Braibant MB, Costagliola S, Rouzioux D, Agut C, Katinger H, Autran H, et al. Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity. AIDS. 2006;20(15):1923–30.CrossRefPubMed

32.

Viveros M, Dickey C, Cotropia JP, Gevorkian G, Larralde C, Broliden K, et al. Characterization of a novel human immunodeficiency virus type 1 neutralizable epitope within the immunodominant region of gp41. Virology. 2000;270(1):135–45.CrossRefPubMed

33.

Zolla-Pazner S, Sharpe S. A resting cell assay for improved detection of antibody-mediated neutralization of HIV type 1 primary isolates. AIDS Res Hum Retrovir. 1995;11(12):1449–58.CrossRefPubMed

34.

Cotropia J, Ugen KE, Kliks S, Broliden K, Broliden PA, Hoxie JA, et al. A human monoclonal antibody to HIV-1 gp41 with neutralizing activity against diverse laboratory isolates. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12(3):221–32.CrossRefPubMed

35.

Cao C, Bai Y, Holloway MJ, Edgeworth RL, Jackson Jr EA, Cotropia J, et al. Characterization of a novel human anti-HIV-1 gp41 IgM monoclonal antibody designated clone 37. DNA Cell Biol. 2004;23(12):836–41.CrossRefPubMed

36.

Nyambi PN, Nadas A, Mbah HA, Burda S, Williams C, Gorny MK, et al. Immunoreactivity of intact virions of human immunodeficiency virus type 1 (HIV-1) reveals the existence of fewer HIV-1 immunotypes than genotypes. J Virol. 2000;74(22):10670–80.CrossRefPubMedCentralPubMed

37.

Moore JP, Cao Y, Qing L, Sattentau QJ, Pyati J, Koduri R, et al. Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol. 1995;69(1):101–9.PubMedCentralPubMed

38.

Kessler 2nd JA, McKenna PM, Emini EA, Chan CP, Patel MD, Gupta SK, et al. Recombinant human monoclonal antibody IgG1b12 neutralizes diverse human immunodeficiency virus type 1 primary isolates. AIDS Res Hum Retrovir. 1997;13(7):575–82.CrossRefPubMed

39.

Parker CE, Deterding LJ, Hager-Braun C, Binley JM, Schulke N, Katinger H, et al. Fine definition of the epitope on the gp41 glycoprotein of human immunodeficiency virus type 1 for the neutralizing monoclonal antibody 2 F5. J Virol. 2001;75(22):10906–11.CrossRefPubMedCentralPubMed

40.

Xu JY, Gorny MK, Palker T, Karwowska S, Zolla-Pazner S. Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. J Virol. 1991;65(9):4832–8.PubMedCentralPubMed

41.

Hioe CE, Xu S, Chigurupati P, Burda S, Williams C, Gorny MK, et al. Neutralization of HIV-1 primary isolates by polyclonal and monoclonal human antibodies. Int Immunol. 1997;9(9):1281–90.CrossRefPubMed

42.

Sattentau QJ, Zolla-Pazner S, Poignard P. Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology. 1995;206(1):713–7.CrossRefPubMed

43.

Cocchi F, DeVico AL, Lu W, Popovic M, Latinovic O, Sajadi MM, et al. Soluble factors from T cells inhibiting X4 strains of HIV are a mixture of β chemokines and RNases. Proc Natl Acad Sci U S A. 2012;109(14):5411–6.CrossRefPubMedCentralPubMed

44.

Kessler M, Kaul A, Santos-Malavé C, Borkowsky W, Kessler J, Shah B. Growth patterns in pubertal HIV-infected adolescents and their correlation with cytokines, IGF-1, IGFBP-1, and IGFBP-3. J Pediatr Endocrinol Metab. 2013;26(7–8):639–44.PubMedCentralPubMed

45.

Toschi E, Barillari G, Sgadari C, Bacigalupo I, Cereseto A, Carlei D, et al. Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix-metalloproteinase in endothelial cells and induction of vascular permeability in vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth factor. Mol Biol Cell. 2001;12(10):2934–46.CrossRefPubMedCentralPubMed

46.

González-Cortés C, Diez-Tascón C, Guerra-Laso JM, González-Cocaño MC, Rivero-Lezcano OM. Non-chemotactic influence of CXCL7 on human phagocytes. Modulation of antimicrobial activity against L. pneumophila. Immunobiol. 2012;217(4):394–401.CrossRef

Title: Identifiable biomarker and treatment development using HIV-1 long term non-progressor sera
Publication date: 01-12-2015
Published in: BMC Immunology / Issue 1/2015
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-015-0094-z

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Conclusions

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